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Results:The results show that the survival rate of mammary epithelial cells were decreasing gradually with the increasing of the time of TGF-β1 treatment, and the survival rates of 24 h and 48 h groups were significantly lower than that of control group (p.05); the LDH activity of 6 h、12 h、24 h and 48 h groups were significantly higher than that of control group (p.05); the DNA degradation arisesed in 12 h, 24 h, and 48 h groups' mammary epithelial cells; the activity of Caspase-3 reach to a peak at 24 h, which was significantly higher than that of control group (p.05); the acinus of epithelial cells appears to break off and collapse with the increasing of treatment time, but the leydig structure keeps integrate;...

结果表明:1、5、10 ng/mL的TGF-β1均能抑制乳腺上皮细胞的增殖,且随浓度增加抑制作用加大,呈现剂量依赖性,其中10 ng/mL TGF-β1组与对照组差异显著(P.05);10 ng/mL TGF-β1作用于乳腺上皮细胞24 h,随作用时间延长细胞凋亡率逐渐增加,6 h、12 h和24 h组与对照组相比差异极显著(P.01);LDH活力也不断升高,6 h、12 h和24 h组与对照组差异显著(P.05);DNA随 TGF-β1作用时间的延长发生不同程度降解;TGF-β1作用2 h~6 h细胞大量表达HSP70,6 h达到高峰,而后下降,2~12 h的表达量均显著高于对照组(P.05)。结论:TGF-β1可以抑制奶牛乳腺上皮细胞的增殖,具有浓度依赖性。10 ng/mLTGF-β1。。。

In summary, our results indicate that hypohidrosis is a frequent adverse effect in children with topiramate therapy. Younger age and hot weather rather than drug dosage are independent risk factors for topiramate-associated hypohidrosis. The resultes also rule out the possibility that topiramate act on its known mechanisms of action, such as potentiating GABA activity at GABAA receptors and antagonizing the AMPA/KA subtype of glutamate receptor in the secretory cells of sweat glands to inhibit sweat secretion. Our data also suggest that topiramate impairs sudomotor function in mice and leads to a significant reduction in AQP5 expression in sweat glands of anhidrotic mice, thus raising the possibility that dysregulation of AQP5 may contribute to topiramate related hypohidrosis. CA inhibition may not be an important contributor since CA II expression and CA activity was intact in anhidrotic mice treated with topiramate.

综合全部实验结果,本研究提示:夏季和低龄是托吡酯引起泌汗障碍的主要危险因素,而托吡酯剂量对泌汗功能的影响较小;托吡酯可以抑制小鼠汗液的分泌,小鼠的年龄并不影响这种抑制作用,但托吡酯对小鼠体温无明显影响;托吡酯并不是通过对GABAA受体及AMPA和KA两种谷氨酸受体亚型的作用而在汗腺分泌细胞抑制泌汗;托吡酯不影响汗腺形态及Na,K-ATP酶活性;汗腺分泌细胞的AQP5功能失调可能与托吡酯引起的泌汗障碍密切相关,而碳酸酐酶抑制作用并不是泌汗功能损害的主要原因。

In summary, our results indicate that hypohidrosis is a frequent adverse effect in children with topiramate therapy. Younger age and hot weather rather than drug dosage are independent risk factors for topiramate-associated hypohidrosis. The resultes also rule out the possibility that topiramate act on its known mechanisms of action, such as potentiating GABA activity at GABAA receptors and antagonizing the AMPA/KA subtype of glutamate receptor in the secretory cells of sweat glands to inhibit sweat secretion. Our data also suggest that topiramate impairs sudomotor function in mice and leads to a significant reduction in AQP5 expression in sweat glands of anhidrotic mice, thus raising the possibility that dysregulation of AQP5 may contribute to topiramate related hypohidrosis.

综合全部实验结果,本研究提示:夏季和低龄是托吡酯引起泌汗障碍的主要危险因素,而托吡酯剂量对泌汗(来源:A44B8787C论文网www.abclunwen.com)功能的影响较小;托吡酯可以抑制小鼠汗液的分泌,小鼠的年龄并不影响这种抑制作用,但托吡酯对小鼠体温无明显影响;托吡酯并不是通过对GABAA受体及AMPA和KA两种谷氨酸受体亚型的作用而在汗腺分泌细胞抑制泌汗;托吡酯不影响汗腺形态及Na,K-ATP酶活性;汗腺分泌细胞的AQP5功能失调可能与托吡酯引起的泌汗障碍密切相关,而碳酸酐酶抑制作用并不是泌汗功能损害的主要原因。

The extent of inhibition of depolarization by superfusion of ethanol for 5 minutes was 41.8±3.3 %(n=17). The addition of 5 nM and 20 nM KT5720 (a selective protein kinase A inhibitor) and 250 μM H9 dihydrochloride (a non-selective protein kinase inhibitor), into the intracellular solution significantly attenuated the inhibitory effects of ethanol.

当分别将5 nM或20 nM KT5720(选择性蛋白质激酶A抑制剂)或250 μM H9 dihydrochoride(非选择性蛋白质激酶抑制剂)置入细胞内液时,乙醇的抑制作用明显被减弱;但乙醇的抑制作用不受到5 nM或20 nM calyculin A(磷酸酶1/2A抑制剂)的影响。

For most viruses,there is aneed for antimicrobials that target unique viral molecular properties.Acycloviris one such drug.It is activated into ahuman herpesvirusDNA polymerase inhibitor exclusively by HHV kinases and,thus,does not suppress other viruses.Here,we show that ACV suppresses HIV-1in HHV-coinfected human tissues,but not in HHV-free tissue or cell cultures.However,addition of HHV-6-infected cells renders these cultures sensitive to anti-HIV ACV activity.We hypothesized that such HIV suppression requires ACV phosphorylation by HHV kinases.Indeed,an ACV monophosphorylated prodrug bypasses the HHV requirement for HIV suppression.Furthermore,phosphorylated ACV directly inhibits HIV-1reverse transcriptase,terminating DNA chain elongation,and can trap RT at the termination site.These data suggest that ACV anti-HIV-1activity may contribute to the response of HIV/HHV-coinfected patients to ACV treatment and could guide strategies for the development of new HIV-1RT inhibitors.

对大多数病毒而言,都需要有针对其分子特性的靶向杀毒剂阿昔洛韦就是这样一种靶向药物在人疱疹病毒酶的特定作用下,阿昔洛韦被激活成为人疱疹病毒DNA聚合酶抑制剂,因此不能再抑制其它的病毒我们的研究发现阿昔洛韦在共感染人疱疹病毒的组织中可以抑制HIV-1,但在无人疱疹病毒感染的组织或细胞中无此作用然而,加入人疱疹病毒-6感染的细胞却使得其对抗HIV的阿昔洛韦变得敏感我们推测这种抑制作用依赖于人疱疹病毒酶导致的阿昔洛韦磷酸化实际上,单磷酸化的阿昔洛韦前体药物无需人疱疹病毒的参与即可抑制HIV此外,磷酸化的阿昔洛韦能直接抑制HIV-1逆转录酶,将其阻止在终止位点,从而终止DNA链的延长这些结果提示阿昔洛韦的抗HIV-1活性决定了艾滋病病毒/人疱疹病毒共感染的患者对阿昔洛韦的治疗反应,也有助于开发新的HIV-1逆转录酶抑制剂

Results:①The amount of human colon carcinoma cell line SW480 treated by quercetin decreased. The morphology of partial SW480 cells was shrunk volume, integrated cell membrane, condensed cytoplasm, pyknotic chromatin, nuclear fragmentation. Apoptotic Corpuscles were found by electron microscope.②MTT colorimetric assay showed quercetin inhibited the growth of human colon carcinoma cell line SW480 in a time- and dose-dependent manner when the concentration of quercetin was 30、60、90μmol/L.③Flow cytometry analysis showed the cell cycle of SW480 cell was restricted in G1/S. G0/G1 phase rate increased and S phase rate decreased with increasing concentration of quercetin and time lasting.④ Zymogram analysis assay showed the secretion of matrix metalloproteinases in human colon carcinoma cell line SW480 treated by quercetin decreased. With increasing concentration of quercetin, the secretion of MMP-2 and MMP-9 decreased.⑤Immunohistochemistry method demonstrated the position expression of Cathepsin-D in SW480 cell was suppressed by quercetin in a time- and dose-dependent manner.

研究结果:经槲皮素处理的人结肠癌SW480细胞数量减少,部分细胞体积缩小,细胞膜完整,胞浆浓缩,核染色质固缩,细胞核碎裂,形成凋亡小体;MTT法检测显示当作用浓度为30μmol/L~90μmol/L时,槲皮素对人结肠癌SW480细胞的生长有抑制作用,其抑制作用随着作用浓度的增加和作用时间的延长而增强;流式细胞学发现槲皮素主要作用于人结肠癌SW480细胞周期的G1/S期,大部分细胞被阻断于S期,随药物浓度的升高和作用时间的延长,G0/G1期细胞比例逐渐增加,S期细胞比例逐渐减少;酶谱分析法检测显示不同浓度的槲皮素能够抑制人结肠癌SW480细胞分泌MMP-2及MMP-9,随浓度的升高,MMP-2及MMP-9的分泌量减少;免疫组织化学法显示不同浓度的槲皮素处理人结肠癌SW480细胞后,Cathepsin-D的表达随药物浓度的升高和作用时间的延长而降低。

Estrogen deficiency can increase the mRNA expression of MMP-1、MMP-3 and IL-1β in OA synovia tissue. Estrogen could inhibit the mRNA expression of MMP-1、 MMP-3 and IL-1β in OA synovia tissue. Progestin could even decrease this expression. Estrogen could slightly increase the mRNA expression of TIMP-1. It is suggested that low dose of estrogen supplement play a protective effect on OA cartilage, and progestin could increase this protective effect.

雌激素缺乏可使OA关节滑膜中MMP-1、MMP-3和IL-1β mRNA表达增加,雌激素对关节滑膜组织中MMP-1、MMP-3和IL-1β mRNA表达有抑制作用,孕激素可增强雌激素的这一抑制作用,雌激素对TIMP-1有轻度升高作用,提示低剂量雌激素对OA关节软骨有一定保护作用,而加用孕激素这一保护作用增强。

Pomegranate juice shows the results of HIV-1 with the corresponding receptors have a strong inhibitory effect, blueberries, blueberry, grape, and sour orange juice a slight inhibitory effect on HIV, but this is not the inhibition of other fruit juices.

结果石榴汁显示出对 HIV-1 与相应受体结合产生较强的抑制作用,蓝莓、越橘、葡萄和酸橙汁对 HIV略有抑制作用,而其他果汁均无此抑制作用。

Injection of rhIL-2 (200,100,50,25,12. 5 ku/kg) can inhibit mouse ear swelling, especially when dosage is 25~50 ku/kg. Injection of rhIL-2 (25 ku/kg) can inhibit rat plantar swelling. The function of mononuclear macrophage system was strengthened by hypodermic injection of rhIL-2( 100 ku/kg) once a day for 9 days. The decrease of mouse delayed-type hypersensitivity reaction induced by cyclophosphamide was extenuated by hypodermic injection of rhIL-2(50 ku/kg) once a day for 6 days. IL-2 has anti-inflammatory effects and immunomodulatory effects when administered in certain dosage.

RhIL-2注射液,剂量为20,10,5,2.5,1.25万u/kg时,对小鼠鼠耳肿胀模型有抑制作用,其中剂量为2.5~5万u/kg时,抑制率最大;剂量为2.5万u/kg时,对大鼠足拓肿胀模型有显著的抑制作用;rhIL-2注射液每日sc用药剂量为10万u/kg,连续给药9d后,可以明显增强小鼠单核吞噬细胞功能;rhIL-2注射液每日sc用药剂量为5万u/kg,连续给药6d后,可明显减轻由免疫抑制剂引起的小鼠迟发性变态反应降低的强度。rhIL-2在一定剂量范围内可以起到抗炎和免疫调节作用。

Results were shown as followings:(1) Sodium selenite at 0~2.5 μmol/L significantly increased the antioxidative capacity of L-02 cells without having remarkable impact on SMMC-7721 cells;(2) Sodium selenite at concentrations above significantly increased telomerase activity, hTERT gene expression and telomere length of L-02 cells without significant impact on SMMC-7721 cells;(3) Sodium selenite at higher concentrations (larger than 5 μmol/L) resulted in peroxidation of L-02 cells, while scutellarin significantly counteracted its effect;(4) Selenium-rich amino acids from silkworm pupas in the range of 0.5~2.5 μmol/L Se significantly inhibited SMMC-7721 cell growth, induced apoptosis and cell cycle change, and the generation of reactive oxygen species. In contrast, sodium selenite and selenomethionine only had weak impact on them at the same concentrations;(5) A new selenium-containing protein was found from selenium-rich silkworm pupas, which is worthy to be study further;(6) An expression vector containing ansense RNA of hTERT gene were constructed and used to transfect SMMC-7721 cells. They were observed to inhibit hepatoma cells.

结果如下:(1)0~2.5μmol/L亚硒酸钠显著性增强L-02细胞的抗氧化能力;而对SMMC-7721细胞的作用不显著;(2)该浓度硒显著性提高L-02细胞端粒酶活性、增强hTERT基因表达和延长细胞端粒长度;而对SMMC-7721细胞的作用均不显著;(3)高浓度硒(5μmol/L以上)显著性抑制L-02细胞生长、致细胞过氧化,灯盏花素能拮抗硒所致过氧化、降低硒毒性;(4)0.5~2.5μmol/L富硒蚕蛹氨基酸显著性抑制肝癌细胞SMMC-7721生长、导致细胞凋亡和周期改变、诱导细胞产生活性氧,同浓度亚硒酸钠和硒代蛋氨酸对其抑制不显著;(5)富硒蚕蛹蛋白经分离纯化和鉴定后发现存在一新含硒蛋白,其结构和功能有待研究;(6)通过已有的含hTERT基因质粒,成功构建hTERT反义RNA表达质粒,转染SMMC-7721细胞后对其生长具有抑制作用。

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