全文获取类型
收费全文 | 5718篇 |
免费 | 546篇 |
出版年
2022年 | 53篇 |
2021年 | 118篇 |
2020年 | 57篇 |
2019年 | 84篇 |
2018年 | 99篇 |
2017年 | 80篇 |
2016年 | 146篇 |
2015年 | 235篇 |
2014年 | 270篇 |
2013年 | 325篇 |
2012年 | 379篇 |
2011年 | 431篇 |
2010年 | 276篇 |
2009年 | 242篇 |
2008年 | 329篇 |
2007年 | 335篇 |
2006年 | 254篇 |
2005年 | 312篇 |
2004年 | 284篇 |
2003年 | 281篇 |
2002年 | 290篇 |
2001年 | 88篇 |
2000年 | 77篇 |
1999年 | 99篇 |
1998年 | 94篇 |
1997年 | 64篇 |
1996年 | 50篇 |
1995年 | 44篇 |
1994年 | 56篇 |
1993年 | 52篇 |
1992年 | 59篇 |
1991年 | 45篇 |
1990年 | 55篇 |
1989年 | 37篇 |
1988年 | 43篇 |
1987年 | 33篇 |
1986年 | 42篇 |
1985年 | 38篇 |
1984年 | 33篇 |
1983年 | 31篇 |
1982年 | 34篇 |
1981年 | 28篇 |
1980年 | 27篇 |
1979年 | 21篇 |
1978年 | 21篇 |
1977年 | 22篇 |
1976年 | 23篇 |
1975年 | 17篇 |
1973年 | 25篇 |
1972年 | 18篇 |
排序方式: 共有6264条查询结果,搜索用时 15 毫秒
1.
2.
3.
4.
5.
6.
Serotonergic status in human blood 总被引:5,自引:0,他引:5
7.
Human Brain Microvascular Endothelial Cells Derived from the BC1 iPS Cell Line Exhibit a Blood-Brain Barrier Phenotype 总被引:1,自引:0,他引:1
The endothelial cells that form capillaries in the brain are highly specialized, with tight junctions that minimize paracellular transport and an array of broad-spectrum efflux pumps that make drug delivery to the brain extremely challenging. One of the major limitations in blood-brain barrier research and the development of drugs to treat central nervous system diseases is the lack of appropriate cell lines. Recent reports indicate that the derivation of human brain microvascular endothelial cells (hBMECs) from human induced pluripotent stem cells (iPSCs) may provide a solution to this problem. Here we demonstrate the derivation of hBMECs extended to two new human iPSC lines: BC1 and GFP-labeled BC1. These hBMECs highly express adherens and tight junction proteins VE-cadherin, ZO-1, occludin, and claudin-5. The addition of retinoic acid upregulates VE-cadherin expression, and results in a significant increase in transendothelial electrical resistance to physiological values. The permeabilities of tacrine, rhodamine 123, and Lucifer yellow are similar to values obtained for MDCK cells. The efflux ratio for rhodamine 123 across hBMECs is in the range 2–4 indicating polarization of efflux transporters. Using the rod assay to assess cell organization in small vessels and capillaries, we show that hBMECs resist elongation with decreasing diameter but show progressive axial alignment. The derivation of hBMECs with a blood-brain barrier phenotype from the BC1 cell line highlights that the protocol is robust. The expression of GFP in hBMECs derived from the BC1-GFP cell line provides an important new resource for BBB research. 相似文献
8.
V P Miller J A Fruetel P R Ortiz de Montellano 《Archives of biochemistry and biophysics》1992,298(2):697-702
trans-1-Phenyl-2-vinylcyclopropane, a hypersensitive radical probe, is oxidized by cytochrome P450cam (CYP101) to a diastereomeric mixture of the corresponding epoxide (81%), (trans-2-phenylcyclopropyl)acetaldehyde (6%), and trans-5-phenyl-2-penten-1,5-diol (13%). trans-5-Phenyl-2-penten-1-ol and (trans-2-phenylcyclopropyl)ethane-1,2-diol are not detectably formed. Authentic standards of all the products have been synthesized and used to establish the identities (or the absence) of the metabolites. Studies with [18O]H2O demonstrate that the oxygens at positions 1 and 5 in the rearranged diol derive from molecular oxygen and water, respectively. Catalytic turnover of the enzyme is required for product formation from the olefin, but incubation of the epoxide metabolite with the enzyme, or with buffer alone, yields both the aldehyde and the rearranged diol products. The absence of trans-5-phenyl-2-penten-1-ol implies that the lifetime of the putative radical intermediate is so short that its existence as a discrete entity is questionable. A cationic intermediate is unlikely but cannot be excluded because the same metabolites are formed in a secondary reaction, even at pH 8.0, from the epoxide. The results provide no evidence for the involvement of radicals or cations in the epoxidation reaction, in agreement with results on the oxidation of olefins in organic solvents by metalloporphyrin catalysts. 相似文献
9.
10.
Jonas G. Barlind Linda K. Buckett Sharon G. Crosby Öjvind Davidsson Hans Emtenäs Anne Ertan Ulrik Jurva Malin Lemurell Pablo Morentin Gutierrez Karolina Nilsson Gavin O’Mahony Annika U. Petersson Alma Redzic Fredrik Wågberg Zhong-Qing Yuan 《Bioorganic & medicinal chemistry letters》2013,23(9):2721-2726
[Acyl CoA]monoacylglycerol acyltransferase 2 (MGAT2) is of interest as a target for therapeutic treatment of diabetes, obesity and other diseases which together constitute the metabolic syndrome. In this Letter we report our discovery and optimisation of a novel series of MGAT2 inhibitors. The development of the SAR of the series and a detailed discussion around some key parameters monitored and addressed during the lead generation phase will be given. The in vivo results from an oral lipid tolerance test (OLTT) using the MGAT2 inhibitor (S)-10, shows a significant reduction (68% inhibition relative to na?ve, p <0.01) in plasma triacylglycerol (TAG) concentration. 相似文献