全文获取类型
收费全文 | 9670篇 |
免费 | 1096篇 |
出版年
2022年 | 82篇 |
2021年 | 205篇 |
2020年 | 105篇 |
2019年 | 129篇 |
2018年 | 150篇 |
2017年 | 138篇 |
2016年 | 256篇 |
2015年 | 423篇 |
2014年 | 439篇 |
2013年 | 522篇 |
2012年 | 612篇 |
2011年 | 661篇 |
2010年 | 421篇 |
2009年 | 380篇 |
2008年 | 502篇 |
2007年 | 480篇 |
2006年 | 484篇 |
2005年 | 459篇 |
2004年 | 407篇 |
2003年 | 365篇 |
2002年 | 325篇 |
2001年 | 204篇 |
2000年 | 194篇 |
1999年 | 164篇 |
1998年 | 102篇 |
1997年 | 84篇 |
1996年 | 68篇 |
1995年 | 80篇 |
1994年 | 76篇 |
1993年 | 83篇 |
1992年 | 141篇 |
1991年 | 137篇 |
1990年 | 140篇 |
1989年 | 123篇 |
1988年 | 109篇 |
1987年 | 112篇 |
1986年 | 85篇 |
1985年 | 88篇 |
1984年 | 82篇 |
1983年 | 104篇 |
1982年 | 68篇 |
1980年 | 42篇 |
1979年 | 74篇 |
1978年 | 62篇 |
1977年 | 60篇 |
1976年 | 63篇 |
1975年 | 41篇 |
1974年 | 50篇 |
1973年 | 54篇 |
1969年 | 51篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
981.
Power JD Cohen AL Nelson SM Wig GS Barnes KA Church JA Vogel AC Laumann TO Miezin FM Schlaggar BL Petersen SE 《Neuron》2011,72(4):665-678
Real-world complex systems may be mathematically modeled as graphs, revealing properties of the system. Here we study graphs of functional brain organization in healthy adults using resting state functional connectivity MRI. We propose two novel brain-wide graphs, one of 264 putative functional areas, the other a modification of voxelwise networks that eliminates potentially artificial short-distance relationships. These graphs contain many subgraphs in good agreement with known functional brain systems. Other subgraphs lack established functional identities; we suggest possible functional characteristics for these subgraphs. Further, graph measures of the areal network indicate that the default mode subgraph shares network properties with sensory and motor subgraphs: it is internally integrated but isolated from other subgraphs, much like a "processing" system. The modified voxelwise graph also reveals spatial motifs in the patterning of systems across the cortex. 相似文献
982.
Damping capacity is evolutionarily conserved in the radial silk of orb-weaving spiders 总被引:1,自引:0,他引:1
Orb-weaving spiders depend upon their two-dimensional silk traps to stop insects in mid flight. While the silks used to construct orb webs must be extremely tough to absorb the tremendous kinetic energy of insect prey, webs must also minimize the return of that energy to prey to prevent insects from bouncing out of oscillating webs. We therefore predict that the damping capacity of major ampullate spider silk, which forms the supporting frames and radial threads of orb webs, should be evolutionarily conserved among orb-weaving spiders. We test this prediction by comparing silk from six diverse species of orb spiders. Silk was taken directly from the radii of orb webs and a Nano Bionix test system was used either to sequentially extend the silk to 25% strain in 5% increments while relaxing it fully between each cycle, or to pull virgin silk samples to 15% strain. Damping capacity was then calculated as the percent difference in loading and unloading energies. Damping capacity increased after yield for all species and typically ranged from 40 to 50% within each cycle for sequentially pulled silk and from 50 to 70% for virgin samples. Lower damping at smaller strains may allow orb webs to withstand minor perturbations from wind and small prey while still retaining the ability to capture large insects. The similarity in damping capacity of silk from the radii spun by diverse spiders highlights the importance of energy absorption by silk for orb-weaving spiders. 相似文献
983.
Powell DA Black WC Bleasby K Chan CC Deschenes D Gagnon M Gordon R Guay J Guiral S Hafey MJ Huang Z Isabel E Leblanc Y Styhler A Xu LJ Zhang L Oballa RM 《Bioorganic & medicinal chemistry letters》2011,21(24):7281-7286
An in vitro screening protocol was used to transform a systemically-distributed SCD inhibitor into a liver-targeted compound. Incorporation of a key nicotinic acid moiety enables molecular recognition by OATP transporters, as demonstrated by uptake studies in transfected cell lines, and likely serves as a critical component of the observed liver-targeted tissue distribution profile. Preclinical anti-diabetic oGTT efficacy is demonstrated with nicotinic acid-based, liver-targeting SCD inhibitor 10, and studies with a close-structural analog devoid of SCD1 activity, suggest this efficacy is a result of on-target activity. 相似文献
984.
McClure KJ Maher M Wu N Chaplan SR Eckert WA Lee DH Wickenden AD Hermann M Allison B Hawryluk N Breitenbucher JG Grice CA 《Bioorganic & medicinal chemistry letters》2011,21(18):5197-5201
The discovery of a series of novel, potent, and selective blockers of the cyclic nucleotide-modulated channel HCN1 is disclosed. Here we report an SAR study around a series of selective blockers of the HCN1 channel. Utilization of a high-throughput VIPR assay led to the identification of a novel series of 2,2-disubstituted indane derivatives, which had moderate selectivity and potency at HCN1. Optimization of this hit led to the identification of the potent, 1,1-disubstituted cyclohexane HCN1 blocker, 2-ethoxy-N-((1-(4-isopropylpiperazin-1-yl)cyclohexyl)methyl)benzamide. The work leading to the discovery of this compound is described herein. 相似文献
985.
Chen Q Bryant VC Lopez H Kelly DL Luo X Natarajan A 《Bioorganic & medicinal chemistry letters》2011,21(7):1929-1932
The quinoxaline core is considered a privileged scaffold as it is found in a variety of biologically relevant molecules. Here we report the synthesis of a quinoxalin-6-amine library, screening against a panel of cancer cell lines and a structure-activity relationship (SAR). This resulted in the identification of a bisfuranylquinoxalineurea analog (7c) that has low micromolar potency against the panel of cancer cell lines. We also show that cells treated with quinoxalineurea 7c results in caspase 3/7 activation, PARP cleavage and Mcl-1 dependent apoptosis. 相似文献
986.
Singh P Sachdeva S Raj R Kumar V Mahajan MP Nasser S Vivas L Gut J Rosenthal PJ Feng TS Chibale K 《Bioorganic & medicinal chemistry letters》2011,21(15):4561-4563
3-Azido-, 3-amino- and 3-(1,2,3-triazol-1-yl)-β-lactams were synthesized and evaluated for their antiplasmodial activity against four strains of Plasmodium falciparum and KB cells for their cytotoxicity profiles. The presence of a cyclohexyl substituent at N-1 and a phenyl group on the triazole ring markedly improved the activity profiles of triazole-tethered β-lactam exhibiting IC50 values of 1.13, 1.21 and 1.00 μM against 3D7, K1 and W2 strains respectively. 相似文献
987.
988.
989.
990.
Kyro K Manandhar SP Mullen D Schmidt WK Distefano MD 《Bioorganic & medicinal chemistry》2011,19(24):7559-7569
Rce1p catalyzes the proteolytic trimming of C-terminal tripeptides from isoprenylated proteins containing CAAX-box sequences. Because Rce1p processing is a necessary component in the Ras pathway of oncogenic signal transduction, Rce1p holds promise as a potential target for therapeutic intervention. However, its mechanism of proteolysis and active site have yet to be defined. Here, we describe synthetic peptide analogues that mimic the natural lipidated Rce1p substrate and incorporate photolabile groups for photoaffinity-labeling applications. These photoactive peptides are designed to crosslink to residues in or near the Rce1p active site. By incorporating the photoactive group via p-benzoyl-l-phenylalanine (Bpa) residues directly into the peptide substrate sequence, the labeling efficiency was substantially increased relative to a previously-synthesized compound. Incorporation of biotin on the N-terminus of the peptides permitted photolabeled Rce1p to be isolated via streptavidin affinity capture. Our findings further suggest that residues outside the CAAX-box sequence are in contact with Rce1p, which has implications for future inhibitor design. 相似文献