全文获取类型
收费全文 | 1819篇 |
免费 | 209篇 |
国内免费 | 1篇 |
专业分类
2029篇 |
出版年
2021年 | 16篇 |
2020年 | 14篇 |
2019年 | 16篇 |
2018年 | 26篇 |
2017年 | 19篇 |
2016年 | 30篇 |
2015年 | 60篇 |
2014年 | 38篇 |
2013年 | 74篇 |
2012年 | 92篇 |
2011年 | 75篇 |
2010年 | 62篇 |
2009年 | 50篇 |
2008年 | 73篇 |
2007年 | 74篇 |
2006年 | 75篇 |
2005年 | 65篇 |
2004年 | 86篇 |
2003年 | 61篇 |
2002年 | 63篇 |
2001年 | 55篇 |
2000年 | 49篇 |
1999年 | 46篇 |
1998年 | 30篇 |
1997年 | 22篇 |
1996年 | 19篇 |
1995年 | 30篇 |
1994年 | 26篇 |
1993年 | 23篇 |
1992年 | 38篇 |
1991年 | 31篇 |
1990年 | 39篇 |
1989年 | 38篇 |
1988年 | 30篇 |
1987年 | 37篇 |
1986年 | 32篇 |
1985年 | 24篇 |
1984年 | 23篇 |
1983年 | 16篇 |
1982年 | 16篇 |
1980年 | 17篇 |
1978年 | 19篇 |
1977年 | 13篇 |
1976年 | 16篇 |
1975年 | 13篇 |
1974年 | 22篇 |
1973年 | 21篇 |
1972年 | 17篇 |
1971年 | 12篇 |
1967年 | 15篇 |
排序方式: 共有2029条查询结果,搜索用时 0 毫秒
941.
Although the acylation of 1-alkenylglycerophosphocholine in mammalian heart is well documented, the acylation of 1-alkenylglycerophosphoethanolamine in the heart was not reported. In this study, the presence of acyl CoA: 1-alkenylglycerophosphoethanolamine acyltransferase in the guinea pig heart microsomes was demonstrated. 1-Alkenylglycerophosphoethanolamine acyltransferase displayed a high degree of specificity towards acyl-CoA. The order of reactivity with acyl-CoA was found to be: linoleoyl much greater than arachidonyl greater than palmitoyl greater than stearoyl = oleoyl. 1-Acylglycerophosphoethanolamine acyltransferase in the microsomes also exhibited specificity towards acyl-CoA in the following manner: linoleoyl greater than arachidonyl much greater than palmitoyl greater than oleoyl greater than stearoyl. However, such specificity appeared to be dependent on acyl-CoA concentration. The acyl-CoA specificities of both enzymes did not correlate with the C-2 acyl distribution observed in the corresponding microsomal phospholipids. Our results suggest that in addition to the acyl specificity of the acyltransferases, intracellular concentrations of acyl-CoAs may also have an important role in determining the observed acyl patterns of the phospholipids. Based on the acyl specificities, pH profiles, and their responses to heat inactivation and thiol reagents, we conclude that 1-alkenylglycerophosphoethanolamine acyltransferase and 1-acylglycerophosphoethanolamine acyltransferase in guinea-pig heart microsomes are not the same enzyme. 相似文献
942.
Proteases are an expanding class of drugs that hold great promise. The U.S. FDA (Food and Drug Administration) has approved 12 protease therapies, and a number of next generation or completely new proteases are in clinical development. Although they are a well-recognized class of targets for inhibitors, proteases themselves have not typically been considered as a drug class despite their application in the clinic over the last several decades; initially as plasma fractions and later as purified products. Although the predominant use of proteases has been in treating cardiovascular disease, they are also emerging as useful agents in the treatment of sepsis, digestive disorders, inflammation, cystic fibrosis, retinal disorders, psoriasis and other diseases. In the present review, we outline the history of proteases as therapeutics, provide an overview of their current clinical application, and describe several approaches to improve and expand their clinical application. Undoubtedly, our ability to harness proteolysis for disease treatment will increase with our understanding of protease biology and the molecular mechanisms responsible. New technologies for rationally engineering proteases, as well as improved delivery options, will expand greatly the potential applications of these enzymes. The recognition that proteases are, in fact, an established class of safe and efficacious drugs will stimulate investigation of additional therapeutic applications for these enzymes. Proteases therefore have a bright future as a distinct therapeutic class with diverse clinical applications. 相似文献
943.
Yang Y Moir E Kontopidis G Taylor P Wear MA Malone K Dunsmore CJ Page AP Turner NJ Walkinshaw MD 《Biochemical and biophysical research communications》2007,363(4):1013-1019
Cyclophilins, which are found in all cellular compartments and with diverse biological roles, are now drug targets for a number of diseases including HIV infection, malaria and ischaemia. We used the database-mining program LIDAEUS and in silico screening to discover the dimedone family of inhibitors which show a conserved ‘ball and socket’ binding mode with a dimethyl group in the hydrophobic binding pocket of human cyclophilin A (CypA) mimicking a key interaction of the natural inhibitor cyclosporin A (CsA). The most potent derivative binds CypA with a Kd of 11.2 ± 9.2 μM and an IC50 for activity against Caenorhabditis elegans (C. elegans) of 190 μM compared to 28 μM for CsA. These dimedone analogues provide a new scaffold for the synthesis of families of peptidomimetic molecules with potential activity against HIV, malaria, and helminth parasite infections. 相似文献
944.
Substantial mortalities of Atlantic salmon (Salmo salar) at two aquaculture sites in Long Island Sound, off Grand Manan Island, Bay of Fundy (BoF) (New Brunswick, Canada) in September 2003, were associated with a bloom of Alexandrium fundyense (>3 × 105 cells L−1), a dinoflagellate alga that produces toxins which cause paralytic shellfish poisoning (PSP). Cells of A. fundyense collected from surface waters while fish were dying had total paralytic shellfish (PS) toxin concentrations of 70.6 pg STX equiv. (saxitoxin equivalents) cell−1 and PS toxin profiles rich in carbamate toxins (78.2%). The zooplankton sampled contained PS toxins (63.1 pg STX equiv. g−1 wet wt) and the toxin profile matched that of A. fundyense cells.Mean PS toxin levels were low (<4 μg STX equiv. 100 g−1 wet wt) in stomach, gill and muscle tissues of moribund salmon, suggesting that PS toxins are very lethal to salmon.The PS toxin concentrations in blue mussels (Mytilus edulis) growing on the salmon cages (37; 526 μg STX equiv. 100 g−1 wet wt) were the highest recorded to date from this region. Their PS toxin profiles showed enhanced carbamate contents (85.5%) compared with that found in A. fundyense. Blue mussels collected from an adjacent Canadian Food Inspection Agency (CFIA) monitoring site in Grand Manan had PS toxin concentrations of 4214 and 150 μg STX equiv. 100 g−1 wet wt in late September and December, respectively, well above the regulatory limit (RL), and horse mussels (Modiolus modiolus) collected in late September had PS toxin concentrations of 2357 μg STX equiv. 100 g−1 wet wt. Detoxification under laboratory conditions suggested that blue mussels may require up to 19 weeks for elimination below RL when they accumulate these high concentrations of PS toxins. This depuration period may be shorter in the field.PS toxin levels above RL were detected in hepatopancreatic tissues of lobster (Homarus americanus), with lower levels (<16 μg STX equiv. 100 g−1 wet wt) in tail muscle and gills.These results illustrate the movement of PS toxins through the marine food chain following an A. fundyense bloom in the BoF, and support earlier studies suggesting that kills from the region of zooplanktivorous fish, such as herring (Clupea harengus harengus), can be attributed to blooms of A. fundyense. This is the first reported incident of PSP associated with mortalities of caged Atlantic salmon in the BoF. Analyses of muscle tissues and viscera from the affected salmon indicated that any portion would not be a health hazard if consumed. 相似文献
945.
946.
947.
948.
949.
In mice, successful development and reproduction require that all cells, including germ cells, transition from a pluripotent to a differentiated state. This transition is associated with silencing of the pluripotency genes Oct4 and Nanog. Interestingly, these genes are repressed at different developmental timepoints in germ and somatic cells. Ovarian germ cells maintain their expression until about embryonic day (E) 14.5, whereas somatic cells silence them much earlier, at about E8.0. In both somatic cells and embryonic stem cells, silencing of Oct4 and Nanog requires the nuclear receptor GCNF. However, expression of the Gcnf gene has not been investigated in fetal ovarian germ cells, and whether it is required for silencing Oct4 and Nanog in that context is not known. Here we demonstrate that Gcnf is expressed in fetal ovarian germ cells, peaking at E14.5, when Oct4 and Nanog are silenced. However, conditional ablation of the ligand-binding domain of Gcnf using a ubiquitous, tamoxifen-inducible Cre indicates that Gcnf is not required for the down-regulation of pluripotency genes in fetal ovarian germ cells, nor is it required for initiation of meiosis and oogenesis. These results suggest that the silencing of Oct4 and Nanog in germ cells occurs via a different mechanism from that operating in somatic cells during gastrulation. 相似文献
950.
Vanessa K. Wong Derek J. Pickard Lars Barquist Karthikeyan Sivaraman Andrew J. Page Peter J. Hart Mark J. Arends Kathryn E. Holt Leanne Kane Lynda F. Mottram Louise Ellison Ruben Bautista Chris J. McGee Sally J. Kay Thomas M. Wileman Linda J. Kenney Calman A. MacLennan Robert A. Kingsley Gordon Dougan 《PloS one》2013,8(12)