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Alterations of integrin α3β1 may play a role in the development of diabetic nephropathy. We have investigated the effects
of high glucose and angiotensin II on the expression of integrin α3 and β1, and whether these changes are associated with
integrin-linked kinase (ILK) in cultured mouse podocytes. Integrin β1 and ILK mRNA expression and protein production were
rapidly up-regulated in a dose-dependent manner by high glucose and angiotensin II stimulation. ILK mRNA levels in the mouse
podocytes exposed to 30 mmol/l glucose were 1.66, 1.89, and 1.28 times higher than those in control cells at 6, 24, and 72 h
exposure, respectively. ILK mRNA levels in mouse podocytes exposed to 1 nM, 10 nM, and 100 nM angiotensin II for 6 h were
1.38, 1.55, and 1.93 times higher, respectively, than those in control cells. Angiotensin-II-induced integrin β1 and ILK mRNA
expression was significantly inhibited by treatment with losartan (100 μM). In addition, the up-regulation of ILK synthesis
induced by these stimuli was related to β1 integrin synthesis and increased ILK kinase activity. Cell adhesion assay displayed
inhibitory effects when podocytes were exposed to high concentrations of angiotensin II. Interestingly, glucose and angiotensin
II stimulation induced shrinkage of the cell body and elongation of the podocyte processes, a phenotype similar to that of
immature podocytes. In addition, β1 integrin showed higher levels of staining on both the cell membranes and the cell-cell
contact areas. Thus, high glucose and angiotensin II may affect the regulation of the integrin-ILK system in podocytes; this
system may therefore play a role in the pathogenesis of diabetic nephropathy and other renal diseases affecting podocytes.
The results presented in this paper have not been published previously in whole or part, except in abstract form.
This work was supported by grant R01–2002–000–00139–0 from the Basic Research Program of the Korea Science & Engineering Foundation. 相似文献
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Characteristics of cold-adaptive endochitinase from Antarctic bacterium Sanguibacter antarcticus KOPRI 21702 总被引:1,自引:0,他引:1
Ha Ju Park Dockyu Kim In Hee Kim Chang-Eun Lee Il-Chan Kim Ju Young Kim Sung Jin Kim Hong Kum Lee Joung Han Yim 《Enzyme and microbial technology》2009,45(5):391-396
The psychrotrophic Sanguibacter antarcticus KOPRI 21702T, isolated from Antarctic seawater, produced a cold-adapted chitinolytic enzyme that is a new 55 kDa family 18 chitinase (Chi21702). Chi21702 exhibited high activities toward pNP-(GlcNAc)2 and pNP-(GlcNAc)3 with no activity for pNP-GlcNAc, indicating that it prefers chitin chains longer than dimers, just as endochitinases do. A mixture of GlcNAc and GlcNAc2 was produced as a main product by Chi21702 activity from chitin oligosaccharides and swollen chitin, while less GlcNAc3 was produced. These results show that Chi21702 has an endochitinase activity, randomly hydrolyzing chitin at internal sites. Chi21702 displayed chitinase activity at 0–40 °C (optimal temperature of 37 °C), maintained its activity at pH 4–11 (optimal pH of 7.6). Interestingly, Chi21702 exhibited relative activities of 40% and 60% at 0 and 10 °C, respectively, in comparison to 100% at 37 °C, which is higher than those of the previously characterized, cold-adapted, chitinases from bacterial strains. 相似文献
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Wang J Zhao B Zhang W Wu X Wang R Huang Y Chen D Park K Weimer BC Shen Y 《Bioorganic & medicinal chemistry letters》2010,20(23):7054-7058
Mycoepoxydiene (MED) is a polyketide isolated from a marine fungus associated with mangrove forests. It contains an oxygen-bridged cyclooctadiene core and an α,β-unsaturated δ-lactone moiety. MED induced the reorganization of cytoskeleton in actively growing HeLa cells by promoting formation of actin stress fiber and inhibiting polymerization of tubulin. MED could induce cell cycle arrest at G2/M in HeLa cells. MED-associated apoptosis was characterized by the formation of fragmented nuclei, PARP cleavage, cytochrome c release, activation of caspase-3, and an increased proportion of sub-G1 cells. Additionally, MED activated MAPK pathways. Interestingly, the time of JNK, p38, and Bcl-2 activation did not correlate with the release of cytochrome c. This study is the first report demonstrating the action mechanism of MED against tumor cell growth. These results provide the potential of MED as a novel low toxic antitumor agent. 相似文献
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