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EDGE (Extraction of Differential Gene Expression) is an open source, point-and-click software program for the significance analysis of DNA microarray experiments. EDGE can perform both standard and time course differential expression analysis. The functions are based on newly developed statistical theory and methods. This document introduces the EDGE software package. 相似文献
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Prakesch M Bijian K Campagna-Slater V Quevillon S Joseph R Wei CQ Sesmilo E Reayi A Poondra RR Barnes ML Leek DM Xu B Lougheed C Schapira M Alaoui-Jamali M Arya P 《Bioorganic & medicinal chemistry》2008,16(21):9596-9602
Inspired by bioactive indoline alkaloid natural products, here, we report a divergent synthesis approach that led to skeletally diverse indoline alkaloid-inspired compounds. The natural product-inspired compounds obtained were then subjected to a series of in vitro and cellular assays to examine their properties as modulators of focal adhesion kinase (FAK) activity. This study resulted in the identification of a promising lead inhibitor of FAK (42), which also showed activity in a wound healing and cell invasion assay. The in silico study of the lead compound (42) was also undertaken. 相似文献
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Null mutations in the glucokinase (GCK) gene can cause autosomal dominant type 2 diabetes (maturity onset diabetes of the young, MODY); however, MODY is genetically heterogeneous. In both liver and pancreatic islet, glucokinase is subject to inhibition by a regulatory protein (GCKR). Given the role of GCK in MODY, GCKR is itself a candidate type 2 diabetes susceptibility gene. Here we describe the structure of full-length (2.2 kb) cDNA for human GCKR, from the hepatoblastoma cell line HepG2. The human GCKR translation product has 625 amino acids and a predicted molecular weight of 68,700. It has 88% amino acid identity to rat GCKR. Yeast artificial chromosomes (YAC clones) containing human GCKR were isolated, and the gene was mapped to Chromosome (Chr) 2p23 by fluorescent in situ hybridization and somatic cell hybrid analysis.EMBL database accession numbers: Z48475 and Z48476. 相似文献
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The inhibition of parotid secretion by pentagastrin increased with dose for jugular and carotid injections (0.01-0.16 micrograms/kg) in acute preparations of 3 sheep anesthetized with sodium pentobarbital. The intracarotid effect exceeded that for the jugular both in magnitude across all doses and in slope relating % inhibition to ln dose (p less than 0.005). The greater depression from carotid injections indicated that the effect was mediated in the head in response to higher pentagastrin concentrations at any dose level. In other experiments, both secretion and associated efferent activity in the parotid nerve were depressed more by carotid than jugular injections of pentagastrin, secretion being reduced by 27.2 vs. 12.1% and efferent activity by 43.2 vs. 20.6% respectively (p less than 0.025). These results indicate that gastrin in the circulation may be able to inhibit parotid secretion in sheep by acting directly on the central nervous system. 相似文献
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We have studied the functional effects of extracellular Cd(2+) on human ether-a-go-go-related gene (HERG) encoded K(+) channels. Low concentrations (10-200 &mgr;M) of extracellular Cd(2+) increased outward currents through HERG channels; 200 &mgr;M Cd(2+) more than doubled HERG currents and altered current kinetics. Cd(2+) concentrations up to 200 &mgr;M did not change the voltage dependence of channel activation, but shifted the voltage dependence of inactivation to more depolarized membrane potentials. Cd(2+) concentrations >/=500 &mgr;M shifted the voltage dependence of channel activation to more positive potentials. These results are consistent with a somewhat specific ability of Cd(2+) to destabilize the inactivated state. We tested the hypothesis that channel inactivation is essential for Cd(2+)-induced increases in HERG K(+) currents, using a double point mutation (G628C/S631C) that diminishes HERG inactivation (Smith, P. L., T. Baukrowitz, and G. Yellen. 1996. Nature (Lond.). 379:833-836). This inactivation-removed mutant is insensitive to low concentrations of Cd(2+). Thus, Cd(2+) had two distinct effects on HERG K(+) channels. Low concentrations of Cd(2+) caused relatively selective effects on inactivation, resulting in a reduction of the apparent rectification of the channel and thereby increasing HERG K(+) currents. Higher Cd(2+) concentrations affected activation gating as well, possibly by a surface charge screening mechanism or by association with a lower affinity site. 相似文献
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James?F?MeschiaEmail author Thomas?G?Brott Robert?D?BrownJr Richard?JP?Crook Michael?Frankel John?Hardy José?G?Merino Stephen?S?Rich Scott?Silliman Bradford?Burke?Worrall 《BMC neurology》2003,3(1):4