全文获取类型
收费全文 | 9591篇 |
免费 | 890篇 |
国内免费 | 1篇 |
出版年
2023年 | 63篇 |
2022年 | 114篇 |
2021年 | 306篇 |
2020年 | 149篇 |
2019年 | 191篇 |
2018年 | 254篇 |
2017年 | 220篇 |
2016年 | 348篇 |
2015年 | 568篇 |
2014年 | 609篇 |
2013年 | 743篇 |
2012年 | 804篇 |
2011年 | 874篇 |
2010年 | 517篇 |
2009年 | 399篇 |
2008年 | 609篇 |
2007年 | 596篇 |
2006年 | 470篇 |
2005年 | 442篇 |
2004年 | 412篇 |
2003年 | 321篇 |
2002年 | 305篇 |
2001年 | 84篇 |
2000年 | 79篇 |
1999年 | 75篇 |
1998年 | 65篇 |
1997年 | 52篇 |
1996年 | 46篇 |
1995年 | 61篇 |
1994年 | 41篇 |
1993年 | 33篇 |
1992年 | 36篇 |
1991年 | 40篇 |
1990年 | 37篇 |
1989年 | 30篇 |
1988年 | 29篇 |
1987年 | 28篇 |
1986年 | 29篇 |
1985年 | 22篇 |
1984年 | 41篇 |
1983年 | 21篇 |
1982年 | 15篇 |
1981年 | 23篇 |
1980年 | 15篇 |
1978年 | 15篇 |
1977年 | 20篇 |
1976年 | 18篇 |
1975年 | 19篇 |
1974年 | 15篇 |
1973年 | 15篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
Zhaolin Wang Cara Fraley Adam R. Mezo 《Bioorganic & medicinal chemistry letters》2013,23(5):1253-1256
The neonatal Fc receptor, FcRn, prolongs the half-life of IgG in the serum and represents a potential therapeutic target for the treatment of autoimmune disease. Small molecules that block the protein–protein interactions of human IgG–human FcRn may lower pathogenic autoantibodies and provide effective treatment. A novel class of quinoxalines has been discovered as antagonists of the IgG:FcRn protein–protein interaction through optimization of a hit derived from a virtual ligand-based screen. 相似文献
2.
3.
Plant and Soil - Cracks and biopores in compacted soil such as plough pans could aid deep rooting, mitigating constraints to seasonal upland use of paddy fields for rice production. This research... 相似文献
4.
When nutrients are depleted, Dictyostelium cells undergo cell cycle arrest and initiate a developmental program that ensures survival. The YakA protein kinase governs this transition by regulating the cell cycle, repressing growth-phase genes and inducing developmental genes. YakA mutants have a shortened cell cycle and do not initiate development. A suppressor of yakA that reverses most of the developmental defects of yakA- cells, but none of their growth defects was identified. The inactivated gene, pufA, encodes a member of the Puf protein family of translational regulators. Upon starvation, pufA- cells develop precociously and overexpress developmentally important proteins, including the catalytic subunit of cAMP-dependent protein kinase, PKA-C. Gel mobility-shift assays using a 200-base segment of PKA-C's mRNA as a probe reveals a complex with wild-type cell extracts, but not with pufA- cell extracts, suggesting the presence of a potential PufA recognition element in the PKA-C mRNA. PKA-C protein levels are low at the times of development when this complex is detectable, whereas when the complex is undetectable PKA-C levels are high. There is also an inverse relationship between PufA and PKA-C protein levels at all times of development in every mutant tested. Furthermore, expression of the putative PufA recognition elements in wild-type cells causes precocious aggregation and PKA-C overexpression, phenocopying a pufA mutation. Finally, YakA function is required for the decline of PufA protein and mRNA levels in the first 4 hours of development. We propose that PufA is a translational regulator that directly controls PKA-C synthesis and that YakA regulates the initiation of development by inhibiting the expression of PufA. Our work also suggests that Puf protein translational regulation evolved prior to the radiation of metazoan species. 相似文献
5.
6.
Hierarchy and monophyly 总被引:1,自引:0,他引:1
7.
Eliot C. Bush Anne E. Clark Chris M. DeBoever Lillian E. Haynes Sidra Hussain Singer Ma Matthew M. McDermott Adam M. Novak John S. Wentworth 《PloS one》2012,7(11)
A significant proportion of enzymes display cooperativity in binding ligand molecules, and such effects have an important impact on metabolic regulation. This is easiest to understand in the case of positive cooperativity. Sharp responses to changes in metabolite concentrations can allow organisms to better respond to environmental changes and maintain metabolic homeostasis. However, despite the fact that negative cooperativity is almost as common as positive, it has been harder to imagine what advantages it provides. Here we use computational models to explore the utility of negative cooperativity in one particular context: that of an inhibitor binding to an enzyme. We identify several factors which may contribute, and show that acting together they can make negative cooperativity advantageous. 相似文献
8.
A Adam J Damas P Franchimont 《Comptes rendus des séances de la Société de biologie et de ses filiales》1980,174(5):856-862
A radioimmunoassay for low molecular weight (LMW) human Kininogen has been carried out. The first step was to prepare LMW Kininogen from human plasma. The proposed method allowed to get chemically pure and biologically active LMW Kininogen. This preparation was used to induce antibody. Optimal conditions for labelling and incubation were determined. This method may be applied to the assay of Kininogen in human plasma. 相似文献
9.
10.
Harjot K. Saini-Chohan Michael G. Holmes Adam J. Chicco William A. Taylor Russell L. Moore Sylvia A. McCune Diane L. Hickson-Bick Grant M. Hatch Genevieve C. Sparagna 《Journal of lipid research》2009,50(8):1600-1608
Cardiolipin (CL) is responsible for modulation of activities of various enzymes involved in oxidative phosphorylation. Although energy production decreases in heart failure (HF), regulation of cardiolipin during HF development is unknown. Enzymes involved in cardiac cardiolipin synthesis and remodeling were studied in spontaneously hypertensive HF (SHHF) rats, explanted hearts from human HF patients, and nonfailing Sprague Dawley (SD) rats. The biosynthetic enzymes cytidinediphosphatediacylglycerol synthetase (CDS), phosphatidylglycerolphosphate synthase (PGPS) and cardiolipin synthase (CLS) were investigated. Mitochondrial CDS activity and CDS-1 mRNA increased in HF whereas CDS-2 mRNA in SHHF and humans, not in SD rats, decreased. PGPS activity, but not mRNA, increased in SHHF. CLS activity and mRNA decreased in SHHF, but mRNA was not significantly altered in humans. Cardiolipin remodeling enzymes, monolysocardiolipin acyltransferase (MLCL AT) and tafazzin, showed variable changes during HF. MLCL AT activity increased in SHHF. Tafazzin mRNA decreased in SHHF and human HF, but not in SD rats. The gene expression of acyl-CoA: lysocardiolipin acyltransferase-1, an endoplasmic reticulum MLCL AT, remained unaltered in SHHF rats. The results provide mechanisms whereby both cardiolipin biosynthesis and remodeling are altered during HF. Increases in CDS-1, PGPS, and MLCL AT suggest compensatory mechanisms during the development of HF. Human and SD data imply that similar trends may occur in human HF, but not during nonpathological aging, consistent with previous cardiolipin studies. 相似文献