全文获取类型
收费全文 | 6335篇 |
免费 | 636篇 |
国内免费 | 1篇 |
出版年
2023年 | 28篇 |
2022年 | 75篇 |
2021年 | 134篇 |
2020年 | 77篇 |
2019年 | 90篇 |
2018年 | 133篇 |
2017年 | 93篇 |
2016年 | 165篇 |
2015年 | 276篇 |
2014年 | 273篇 |
2013年 | 381篇 |
2012年 | 456篇 |
2011年 | 386篇 |
2010年 | 275篇 |
2009年 | 258篇 |
2008年 | 364篇 |
2007年 | 379篇 |
2006年 | 308篇 |
2005年 | 273篇 |
2004年 | 283篇 |
2003年 | 258篇 |
2002年 | 199篇 |
2001年 | 99篇 |
2000年 | 98篇 |
1999年 | 91篇 |
1998年 | 82篇 |
1997年 | 51篇 |
1996年 | 53篇 |
1995年 | 65篇 |
1994年 | 47篇 |
1993年 | 53篇 |
1992年 | 69篇 |
1991年 | 68篇 |
1990年 | 59篇 |
1989年 | 55篇 |
1988年 | 51篇 |
1987年 | 38篇 |
1986年 | 40篇 |
1985年 | 62篇 |
1984年 | 56篇 |
1983年 | 41篇 |
1982年 | 39篇 |
1981年 | 46篇 |
1980年 | 32篇 |
1979年 | 50篇 |
1978年 | 34篇 |
1976年 | 34篇 |
1974年 | 28篇 |
1973年 | 29篇 |
1971年 | 27篇 |
排序方式: 共有6972条查询结果,搜索用时 31 毫秒
1.
L-myo-Inositol-1-phosphate synthase has been found to have at least a 5-fold preference for the beta-anomer of its natural substrate D-Glc-6-P. The alpha-anomer appears to be an inhibitor of the reaction and may be converted to product as well. As well as showing an enzymatic preference for the equatorial C-1 hydroxyl of D-Glc-6-P, our results suggest that it is the pyranose form of D-Glc-6-P that binds to the enzyme and that ring-opening is an enzymatic step. We have also found D-2-dGlc-6-P, D-2-F-2-dGlc-6-P, and D-Man-6-P each to be both competitive inhibitors and substrates that are converted to inositol phosphates by the synthase. D-Allose-6-P is a weak inhibitor of the enzyme, but not a substrate. D-Gal-6-P is neither substrate nor inhibitor. Thus the specificity of the synthase with respect to single position epimers of D-Glc-6-P increases in the order C1 less than C2 much less than C3 less than C4. 相似文献
2.
3.
4.
5.
The existence of an optimal range of cytosolic free calcium for insulin-stimulated glucose transport in rat adipocytes 总被引:9,自引:0,他引:9
B Draznin K Sussman M Kao D Lewis N Sherman 《The Journal of biological chemistry》1987,262(30):14385-14388
We have examined the effects of extracellular and intracellular Ca2+ concentrations upon basal and insulin-stimulated 2-deoxyglucose uptake in isolated rat adipocytes. In the absence of extracellular Ca2+, both basal and insulin-stimulated glucose uptake were significantly reduced. Insulin-stimulated glucose transport was optimal at 1 and 2 mM Ca2+. Further increases in extracellular Ca2+ concentration (3 mM) significantly diminished insulin-stimulated glucose uptake. When intracellular Ca2+ concentrations were augmented by ionomycin (1 microM), insulin-stimulated glucose uptake was significantly reduced at extracellular Ca2+ concentrations of 2 and 3 mM. The levels of intracellular free Ca2+ concentrations were then measured with Ca2+ indicator fura-2. The correlation between the levels of intracellular free Ca2+ and the magnitude of insulin-stimulated glucose uptake revealed that the optimal effect of insulin is observed at Ca2+ levels between 140 and 370 nM. At both extremes outside of this window, both low and high levels of intracellular Ca2+ result in diminished cellular responsiveness to insulin. These data suggest that intracellular calcium concentrations may exert a dual role in the regulation of cellular sensitivity to insulin. First, there must exist a minimal concentration of intracellular calcium to promote insulin action. Second, increased levels of intracellular calcium may provide a critical signal for diminution of insulin action. 相似文献
6.
7.
This study presents an approach to identifying surface residues on membrane proteins that are exposed toward the membrane-aqueous interface. The method employs a lipid Ni(II) chelate that localizes the metal ion to a region near the membrane-aqueous interface. Lateral diffusion of the lipid chelate results in Heisenberg exchange (HE) with nitroxide side chains in the protein only if direct contact occurs between the paramagnetic species during a collision. Thus, HE serves as a signature for residues facing the bilayer in the neighborhood of the membrane-aqueous interface. To evaluate the method, 13 surface residues on the extracellular half of KcsA, a prokaryotic potassium channel of known structure, were examined for HE with the Ni(II) chelate. The HE rate between the two species is found to depend strongly on the vertical position of the nitroxide with respect to the membrane-aqueous interface. Nitroxides introduced near the interface experience relatively high HE rates, whereas nitroxides that are immersed in the bilayer interior or sterically sheltered from collision experience low or undetectable rates. The results indicate that residues near the interface can be identified on the basis of their high rates of collision with the headgroup region of the bilayer. 相似文献
8.
9.
Alicia P. Higueruelo Adrian Schreyer G. Richard J Bickerton Tom L. Blundell Will R. Pitt 《PloS one》2012,7(12)
Efforts to increase affinity in the design of new therapeutic molecules have tended to lead to greater lipophilicity, a factor that is generally agreed to be contributing to the low success rate of new drug candidates. Our aim is to provide a structural perspective to the study of lipophilic efficiency and to compare molecular interactions created over evolutionary time with those designed by humans. We show that natural complexes typically engage in more polar contacts than synthetic molecules bound to proteins. The synthetic molecules also have a higher proportion of unmatched heteroatoms at the interface than the natural sets. These observations suggest that there are lessons to be learnt from Nature, which could help us to improve the characteristics of man-made molecules. In particular, it is possible to increase the density of polar contacts without increasing lipophilicity and this is best achieved early in discovery while molecules remain relatively small. 相似文献
10.
Adrian C. Kanaar 《BMJ (Clinical research ed.)》1941,1(4188):549-552