全文获取类型
收费全文 | 2288篇 |
免费 | 234篇 |
国内免费 | 1篇 |
出版年
2023年 | 16篇 |
2022年 | 28篇 |
2021年 | 54篇 |
2020年 | 27篇 |
2019年 | 33篇 |
2018年 | 46篇 |
2017年 | 40篇 |
2016年 | 56篇 |
2015年 | 80篇 |
2014年 | 94篇 |
2013年 | 143篇 |
2012年 | 135篇 |
2011年 | 126篇 |
2010年 | 77篇 |
2009年 | 79篇 |
2008年 | 96篇 |
2007年 | 82篇 |
2006年 | 74篇 |
2005年 | 96篇 |
2004年 | 87篇 |
2003年 | 76篇 |
2002年 | 78篇 |
2001年 | 43篇 |
2000年 | 48篇 |
1999年 | 44篇 |
1998年 | 38篇 |
1997年 | 35篇 |
1996年 | 26篇 |
1995年 | 30篇 |
1994年 | 27篇 |
1993年 | 24篇 |
1992年 | 33篇 |
1991年 | 37篇 |
1990年 | 40篇 |
1989年 | 25篇 |
1988年 | 24篇 |
1987年 | 31篇 |
1986年 | 22篇 |
1985年 | 19篇 |
1983年 | 17篇 |
1982年 | 18篇 |
1981年 | 17篇 |
1979年 | 19篇 |
1978年 | 20篇 |
1977年 | 16篇 |
1973年 | 15篇 |
1971年 | 16篇 |
1969年 | 14篇 |
1968年 | 15篇 |
1967年 | 16篇 |
排序方式: 共有2523条查询结果,搜索用时 31 毫秒
821.
Aspiotis R Chen A Cauchon E Dubé D Falgueyret JP Gagné S Gallant M Grimm EL Houle R Juteau H Lacombe P Laliberté S Lévesque JF MacDonald D McKay D Percival MD Roy P Soisson SM Wu T 《Bioorganic & medicinal chemistry letters》2011,21(8):2430-2436
The incorporation of a carboxylic acid within in a series of 3-amido-4-aryl substituted piperidines (represented by general structure 32) led to the discovery of potent, zwitterionic, renin inhibitors with improved off-target profiles (CYP3A4 time-dependent inhibition and hERG affinity) relative to analogous non-zwitterionic inhibitors of the past (i.e., 3). Strategies to address the oral absorption of these zwitterions are also discussed within. 相似文献
822.
823.
Leng L Chen L Fan J Greven D Arjona A Du X Austin D Kashgarian M Yin Z Huang XR Lan HY Lolis E Nikolic-Paterson D Bucala R 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(1):527-538
Autoimmunity leads to the activation of innate effector pathways, proinflammatory cytokine production, and end-organ injury. Macrophage migration inhibitory factor (MIF) is an upstream activator of the innate response that mediates the recruitment and retention of monocytes via CD74 and associated chemokine receptors, and it has a role in the maintenance of B lymphocytes. High-expression MIF alleles also are associated with end-organ damage in different autoimmune diseases. We assessed the therapeutic efficacy of (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), an orally bioavailable MIF antagonist, in two distinct models of systemic lupus erythematosus: the NZB/NZW F1 and the MRL/lpr mouse strains. ISO-1, like anti-MIF, inhibited the interaction between MIF and its receptor, CD74, and in each model of disease, it reduced functional and histological indices of glomerulonephritis, CD74(+) and CXCR4(+) leukocyte recruitment, and proinflammatory cytokine and chemokine expression. Neither autoantibody production nor T and B cell activation were significantly affected, pointing to the specificity of MIF antagonism in reducing excessive proinflammatory responses. These data highlight the feasibility of targeting the MIF-MIF receptor interaction by small-molecule antagonism and support the therapeutic value of downregulating MIF-dependent pathways of tissue damage in systemic lupus erythematosus. 相似文献
824.
825.
Nanavati D Austin DR Catapano LA Luckenbaugh DA Dosemeci A Manji HK Chen G Markey SP 《Journal of neurochemistry》2011,119(3):617-629
Bipolar disorder is a devastating illness that is marked by recurrent episodes of mania and depression. There is growing evidence that the disease is correlated with disruptions in synaptic plasticity cascades involved in cognition and mood regulation. Alleviating the symptoms of bipolar disorder involves chronic treatment with mood stabilizers like lithium or valproate. These two structurally dissimilar drugs are known to alter prominent signaling cascades in the hippocampus, but their effects on the post-synaptic density complex remain undefined. In this work, we utilized mass spectrometry for quantitative profiling of the rat hippocampal post-synaptic proteome to investigate the effects of chronic mood stabilizer treatment. Our data show that in response to chronic treatment of mood stabilizers there were not gross qualitative changes but rather subtle quantitative perturbations in post-synaptic density proteome linked to several key signaling pathways. Our data specifically support the changes in actin dynamics on valproate treatment. Using label-free quantification methods, we report that lithium and valproate significantly altered the abundance of 21 and 43 proteins, respectively. Seven proteins were affected similarly by both lithium and valproate: Ank3, glutamate receptor 3, dynein heavy chain 1, and four isoforms of the 14-3-3 family. Immunoblotting the same samples confirmed the changes in Ank3 and glutamate receptor 3 abundance. Our findings support the hypotheses that BPD is a synaptic disorder and that mood stabilizers modulate the protein signaling complex in the hippocampal post-synaptic density. 相似文献
826.
McKinniss EN Esterman RD Woodall SA Austin BR Hersom MJ Thatcher WW Yelich JV 《Theriogenology》2011,75(9):1699-1707
Yearling Bos indicus × Bos taurus heifers (n = 410) from three locations, were synchronized with either the Select Synch/CIDR+timed-AI (SSC+TAI) or 7-11+timed-AI (7-11+TAI) treatments. On Day 0 of the experiment, within each location, heifers were equally distributed to treatments by reproductive tract score (RTS; Scale 1-5: 1 = immature, 5 = estrous cycling) and body condition score. The 7-11+TAI treatment consisted of melengestrol acetate (0.5 mg/head/d) from Days 0 to 7, with PGF2α (25 mg im) on Day 7, GnRH (100 μg im) on Day 11, and PGF2α (25 mg im) on Day 18. The SSC+TAI heifers received the same carrier supplement (without MGA) from Days 0 to 7, and on Day 11 they were given 100 μg GnRH and an intravaginal CIDR (containing 1.38 g progesterone). The CIDR were removed on Day 18, concurrent with 25 mg PGF2α im For both treatments, estrus was visually detected for 1 h twice daily (0700 and 1600 h) for 72 h after PGF2α, with AI done 6 to 12 h after a detected estrus. Non-responders were timed-AI and received GnRH (100 μg im) 72 to 76 h post PGF2α. The 7-11+TAI heifers had a greater (P < 0.05) estrous response (55.2 vs 41.9%), conception rate (47.0 vs 31.3%), and synchronized pregnancy rate (33.5 vs 24.8%) compared to SSC+TAI heifers, respectively. Heifers exhibiting estrus at 60 h (61.7%) had a greater (P < 0.05) conception rate compared to heifers that exhibited estrus at ≤ 36 (35.3%), 48 (31.6%), and 72 h (36.2%), which were similar (P > 0.05) to each other. As RTS increased from ≤ 2 to ≥ 3, estrous response, conception rate, synchronized pregnancy rate, and 30 d pregnancy rate all increased (P < 0.05), irrespective of synchronization treatment. In conclusion, the 7-11+TAI treatment yielded greater synchronized pregnancy rates compared to SSC+TAI treatment in yearling Bos indicus × Bos taurus heifers. 相似文献
827.
Young E Poucher A Comer A Bailey A Alper H 《Applied and environmental microbiology》2011,77(10):3311-3319
Molecular transport is a key process in cellular metabolism. This step is often limiting when using a nonnative carbon source, as exemplified by xylose catabolism in Saccharomyces cerevisiae. As a step toward addressing this limitation, this study seeks to characterize monosaccharide transport preference and efficiency. A group of 26 known and putative monosaccharide transport proteins was expressed in a recombinant Saccharomyces cerevisiae host unable to transport several monosaccharides. A growth-based assay was used to detect transport capacity across six different carbon sources (glucose, xylose, galactose, fructose, mannose, and ribose). A mixed glucose-and-xylose cofermentation was performed to determine substrate preference. These experiments identified 10 transporter proteins that function as transporters of one or more of these sugars. Most of these proteins exhibited broad substrate ranges, and glucose was preferred in all cases. The broadest transporters confer the highest growth rates and strongly prefer glucose. This study reports the first molecular characterization of the annotated XUT genes of Scheffersomyces stipitis and open reading frames from the yeasts Yarrowia lipolytica and Debaryomyces hansenii. Finally, a phylogenetic analysis demonstrates that transporter function clusters into three distinct groups. One particular group comprised of D. hansenii XylHP and S. stipitis XUT1 and XUT3 demonstrated moderate transport efficiency and higher xylose preferences. 相似文献
828.
829.
830.
Sergey A Belokobylskij Muhammad Iqbal † Andrew D Austin 《Australian Journal of Entomology》2003,42(3):260-265
Abstract The subfamily Dirrhopinae (Hymenoptera: Braconidae) is recorded for the first time from the Australian region on the basis of Dirrhope minor Belokobylskij collected at light from several sites in northern Queensland. The species is redescribed and a discussion of relationships, distribution and biology of the subfamily is presented. 相似文献