全文获取类型
收费全文 | 111篇 |
免费 | 3篇 |
专业分类
114篇 |
出版年
2022年 | 1篇 |
2021年 | 1篇 |
2018年 | 1篇 |
2015年 | 4篇 |
2013年 | 6篇 |
2012年 | 5篇 |
2011年 | 1篇 |
2010年 | 4篇 |
2009年 | 2篇 |
2008年 | 4篇 |
2007年 | 1篇 |
2006年 | 3篇 |
2005年 | 7篇 |
2004年 | 1篇 |
2003年 | 5篇 |
2002年 | 1篇 |
2001年 | 7篇 |
2000年 | 7篇 |
1999年 | 4篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1994年 | 1篇 |
1992年 | 5篇 |
1991年 | 1篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1977年 | 1篇 |
1975年 | 3篇 |
1974年 | 1篇 |
1973年 | 3篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 3篇 |
1969年 | 2篇 |
1965年 | 1篇 |
排序方式: 共有114条查询结果,搜索用时 15 毫秒
51.
Inhibition of rat brain glutamate decarboxylase (GAD, EC 4.1.1.15) by individual stereoisomers of 4-fluoroglutamate (4-F-Glu) and 2-fluoro-4-aminobutyrate (2-F-GABA) was studied. All stereoisomers of 4-F-Glu inhibited decarboxylation of L-glutamate catalysed by the enzyme preparation. At 1 x 10(-2) M concentration, the most potent inhibitor of GAD was D-erythro-4-F-Glu with about 70% inhibition in the presence of 1.23 x 10(-2)M L-glutamate. The inhibition by all stereoisomers was of the competitive type. Ki values ranged from 2 x 10(-3)M for the D-erythro isomer to 1.1 x 10(-2)M for the D-threo and L-erythro isomers. The influence of all stereoisomers was reversible as shown by dialysis except for a small amount in the case of the D-erythro isomer. The inhibition was independent of external pyridoxal-5'-phosphate added. No inhibition of rat brain GAD was found with 2-fluoro-4-aminobutyrate stereoisomers. 相似文献
52.
Pankaj Kumar Pearl Magala Kathryn?R. Geiger-Schuller Ananya Majumdar Joel R. Tolman Cynthia Wolberger 《Nucleic acids research》2015,43(18):9039-9050
Rad6 is a yeast E2 ubiquitin conjugating enzyme that monoubiquitinates histone H2B in conjunction with the E3, Bre1, but can non-specifically modify histones on its own. We determined the crystal structure of a Rad6∼Ub thioester mimic, which revealed a network of interactions in the crystal in which the ubiquitin in one conjugate contacts Rad6 in another. The region of Rad6 contacted is located on the distal face of Rad6 opposite the active site, but differs from the canonical E2 backside that mediates free ubiquitin binding and polyubiquitination activity in other E2 enzymes. We find that free ubiquitin interacts weakly with both non-canonical and canonical backside residues of Rad6 and that mutations of non-canonical residues have deleterious effects on Rad6 activity comparable to those observed to mutations in the canonical E2 backside. The effect of non-canonical backside mutations is similar in the presence and absence of Bre1, indicating that contacts with non-canonical backside residues govern the intrinsic activity of Rad6. Our findings shed light on the determinants of intrinsic Rad6 activity and reveal new ways in which contacts with an E2 backside can regulate ubiquitin conjugating activity. 相似文献
53.
54.
Activation of PPARdelta alters lipid metabolism in db/db mice 总被引:11,自引:0,他引:11
Leibowitz MD Fiévet C Hennuyer N Peinado-Onsurbe J Duez H Bergera J Cullinan CA Sparrow CP Baffic J Berger GD Santini C Marquis RW Tolman RL Smith RG Moller DE Auwerx J 《FEBS letters》2000,473(3):333-336
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors, which heterodimerize with the retinoid X receptor and bind to peroxisome proliferator response elements in the promoters of regulated genes. Despite the wealth of information available on the function of PPARalpha and PPARgamma, relatively little is known about the most widely expressed PPAR subtype, PPARdelta. Here we show that treatment of insulin resistant db/db mice with the PPARdelta agonist L-165041, at doses that had no effect on either glucose or triglycerides, raised total plasma cholesterol concentrations. The increased cholesterol was primarily associated with high density lipoprotein (HDL) particles, as shown by fast protein liquid chromatography analysis. These data were corroborated by the chemical analysis of the lipoproteins isolated by ultracentrifugation, demonstrating that treatment with L-165041 produced an increase in circulating HDL without major changes in very low or low density lipoproteins. White adipose tissue lipoprotein lipase activity was reduced following treatment with the PPARdelta ligand, but was increased by a PPARgamma agonist. These data suggest both that PPARdelta is involved in the regulation of cholesterol metabolism in db/db mice and that PPARdelta ligands could potentially have therapeutic value. 相似文献
55.
56.
Georgianna S. Harris Kenneth Ellsworth Bruce E. Witzel Richard L. Tolman 《Bioorganic chemistry》1996,24(4):386-400
Two nonsteroids, ONO-3805 and LY191704, were evaluated as inhibitors of the human and rat 5α-reductases (5αR). ONO-3805 was prepared in a 12-step convergent synthesis. This compound is a potent inhibitor of the human and rat 5αRs, with more potent inhibition seen against the rat enzymes. The inhibition patterns of this compound were best fit to an uncompetitive model which suggests binding in a ternary complex with enzyme and NADP+. ApparentKivalues of 27, 31, 1, and 0.5 n$of5$M versus testosterone were obtained with human type 1, human type 2, rat type 1, and rat type 2 5αR, respectively. Multiple inhibition studies with ONO-3805 and NADP+support synergistic binding of these two inhibitors with all isozymes. LY191704 was also evaluated as an inhibitor of the human and rat 5αRs. This compound is a selective, competitive inhibitor of human type 1 5αR. Poor inhibition was observed with human type 2 and rat types 1 and 2 5αR. 相似文献
57.
Sara Konrath Emily Falk Andrea Fuhrel-Forbis Mary Liu James Swain Richard Tolman Rebecca Cunningham Maureen Walton 《PloS one》2015,10(9)
To what extent can simple mental exercises cause shifts in empathic habits? Can we use mobile technology to make people more empathic? It may depend on how empathy is measured. Scholars have identified a number of different facets and correlates of empathy. This study is among the first to take a comprehensive, multidimensional approach to empathy to determine how empathy training could affect these different facets and correlates. In doing so, we can learn more about empathy and its multifaceted nature. Participants (N = 90) were randomly assigned to receive either an empathy-building text message program (Text to Connect) or one of two control conditions (active versus passive). Respondents completed measures of dispositional empathy (i.e. self-perceptions of being an empathic person), affective empathy (i.e. motivations to help, immediate feelings of empathic concern), and prosocial behavior (i.e. self-reports and observer-reports) at baseline, and then again after the 14 day intervention period. We found that empathy-building messages increased affective indicators of empathy and prosocial behaviors, but actually decreased self-perceptions of empathy, relative to control messages. Although the brief text messaging intervention did not consistently impact empathy-related personality traits, it holds promise for the use of mobile technology for changing empathic motivations and behaviors. 相似文献
58.
J R Tolman 《Current opinion in structural biology》2001,11(5):532-539
The introduction of residual dipolar coupling methodology has increased the scope of structural biological problems that can be addressed by NMR spectroscopy. Conformational changes, the relative orientation of domains, and intermolecular complexes can now be characterized accurately and rapidly using NMR. The development of residual dipolar coupling methodology for the rapid recognition of homologous protein folds and for studies of submillisecond timescale dynamics has also seen considerable progress. 相似文献
59.
Several non-steroidal anti-inflammatory agents (NSAIA) are shown to inhibit the net production of prostaglandin (PG)- like activity from arachidonic acid by a cell-free preparation of guinea-pig lung. Moreover, these agents also antagonize PGE1-induced contractions of the isolated gerbil colon. The anti-spasmogenic effects are reversible and specific. At high concentrations, indomethacin and mefenamic acid interfere with the binding of PGE1 to a broken cell preparation of rat epididymal adipocytes. Taken together the data indicate that NSAIA interact with prostaglandins at multiple sites and are consistent with the suggestions reported previously that NSAIA may have multiple
actions. 相似文献
60.