全文获取类型
收费全文 | 5531篇 |
免费 | 476篇 |
国内免费 | 4篇 |
出版年
2023年 | 26篇 |
2022年 | 73篇 |
2021年 | 130篇 |
2020年 | 58篇 |
2019年 | 71篇 |
2018年 | 92篇 |
2017年 | 77篇 |
2016年 | 140篇 |
2015年 | 216篇 |
2014年 | 228篇 |
2013年 | 286篇 |
2012年 | 403篇 |
2011年 | 320篇 |
2010年 | 220篇 |
2009年 | 181篇 |
2008年 | 293篇 |
2007年 | 293篇 |
2006年 | 254篇 |
2005年 | 227篇 |
2004年 | 226篇 |
2003年 | 183篇 |
2002年 | 169篇 |
2001年 | 184篇 |
2000年 | 162篇 |
1999年 | 129篇 |
1998年 | 52篇 |
1997年 | 44篇 |
1996年 | 28篇 |
1995年 | 38篇 |
1994年 | 36篇 |
1993年 | 35篇 |
1992年 | 92篇 |
1991年 | 77篇 |
1990年 | 80篇 |
1989年 | 84篇 |
1988年 | 61篇 |
1987年 | 62篇 |
1986年 | 68篇 |
1985年 | 68篇 |
1984年 | 54篇 |
1983年 | 49篇 |
1982年 | 40篇 |
1981年 | 28篇 |
1980年 | 31篇 |
1979年 | 42篇 |
1978年 | 31篇 |
1976年 | 27篇 |
1975年 | 27篇 |
1974年 | 34篇 |
1973年 | 36篇 |
排序方式: 共有6011条查询结果,搜索用时 15 毫秒
991.
Muse Oke Lester G. Carter Kenneth A. Johnson Huanting Liu Stephen A. McMahon Xuan Yan Melina Kerou Nadine D. Weikart Nadia Kadi Md. Arif Sheikh Stefan Schmelz Mark Dorward Michal Zawadzki Christopher Cozens Helen Falconer Helen Powers Ian M. Overton C. A. Johannes van Niekerk Xu Peng Prakash Patel Roger A. Garrett David Prangishvili Catherine H. Botting Peter J. Coote David T. F. Dryden Geoffrey J. Barton Ulrich Schwarz-Linek Gregory L. Challis Garry L. Taylor Malcolm F. White James H. Naismith 《Journal of structural and functional genomics》2010,11(2):167-180
The Scottish Structural Proteomics Facility was funded to develop a laboratory scale approach to high throughput structure determination. The effort was successful in that over 40 structures were determined. These structures and the methods harnessed to obtain them are reported here. This report reflects on the value of automation but also on the continued requirement for a high degree of scientific and technical expertise. The efficiency of the process poses challenges to the current paradigm of structural analysis and publication. In the 5 year period we published ten peer-reviewed papers reporting structural data arising from the pipeline. Nevertheless, the number of structures solved exceeded our ability to analyse and publish each new finding. By reporting the experimental details and depositing the structures we hope to maximize the impact of the project by allowing others to follow up the relevant biology. 相似文献
992.
G-quadruplexes and Z-DNA are two important non-B forms of DNA architecture. Results on novel structural elements, folding and unfolding kinetics, and interactions with small molecules and proteins have been reported recently for these forms. These results will enhance our understanding of the biology of these structures and provide a platform for drug design. 相似文献
993.
The CLAVATA1-related BAM1, BAM2 and BAM3 receptor kinase-like proteins are required for meristem function in Arabidopsis 总被引:1,自引:0,他引:1
DeYoung BJ Bickle KL Schrage KJ Muskett P Patel K Clark SE 《The Plant journal : for cell and molecular biology》2006,48(1):1-16
Organ formation at shoot and flower meristems in plants requires the maintenance of a population of centrally located stem cells and the differentiation of peripherally located daughter cells. The CLAVATA (CLV) gene products in Arabidopsis, including the CLV1 receptor-kinase, regulate this process by promoting the differentiation of stem cells on the meristem flanks. Here, we have analyzed the developmental roles of the CLV1-related BAM1 (derived from barely any meristem 1), BAM2 and BAM3 receptor-like kinases. Loss-of-function alleles of these receptors lead to phenotypes consistent with the loss of stem cells at the shoot and flower meristem, suggesting that their developmental role is opposite to that of CLV1. These closely related receptors are further distinguished from CLV1, whose expression and function is highly specific, by having broad expression patterns and multiple developmental roles. These include a requirement for BAM1, BAM2 and BAM3 in the development of high-ordered vascular strands within the leaf and a correlated control of leaf shape, size and symmetry. In addition, BAM1, BAM2 and BAM3 are required for male gametophyte development, as well as ovule specification and function. Significantly, the differing roles of CLV1 and BAM receptors in meristem and organ development are largely driven by differences in expression patterns. 相似文献
994.
Bamborough P Christopher JA Cutler GJ Dickson MC Mellor GW Morey JV Patel CB Shewchuk LM 《Bioorganic & medicinal chemistry letters》2006,16(24):6236-6240
The identification and hit-to-lead exploration of a novel, potent and selective series of substituted benzimidazole–thiophene carbonitrile inhibitors of IKK-ε kinase is described. Compound 12e was identified with an IKK-ε enzyme potency of pIC50 7.4, and has a highly encouraging wider selectivity profile, including selectivity within the IKK kinase family. 相似文献
995.
Yin Z Patel SJ Wang WL Chan WL Ranga Rao KR Wang G Ngew X Patel V Beer D Knox JE Ma NL Ehrhardt C Lim SP Vasudevan SG Keller TH 《Bioorganic & medicinal chemistry letters》2006,16(1):40-43
With the aim of discovering potent and selective dengue NS3 protease inhibitors, we systematically synthesized and evaluated a series of tetrapeptide aldehydes based on lead aldehyde 1 (Bz-Nle-Lys-Arg-Arg-H, K(i)=5.8 microM). In general, we observe that interactions of P(2) side chain are more important than P(1) followed by P(3) and P(4). Tripeptide and dipeptide aldehyde inhibitors also show low micromolar activity. Additionally, an effective non-basic, uncharged replacement of P(1) Arg is identified. 相似文献
996.
Xu J Wei L Mathvink R Edmondson SD Mastracchio A Eiermann GJ He H Leone JF Leiting B Lyons KA Marsilio F Patel RA Petrov A Wu JK Thornberry NA Weber AE 《Bioorganic & medicinal chemistry letters》2006,16(5):1346-1349
anti-Substituted beta-methylphenylalanine derived amides have been shown to be potent DPP-IV inhibitors exhibiting excellent selectivity over both DPP8 and DPP9. The optimized compound exhibited good pharmacokinetic profiles in three preclinical species. 相似文献
997.
Yeh VS Patel JR Yong H Kurukulasuriya R Fung S Monzon K Chiou W Wang J Stolarik D Imade H Beno D Brune M Jacobson P Sham H Link JT 《Bioorganic & medicinal chemistry letters》2006,16(20):5414-5419
A series of metabolically stable adamantane amide 11beta-HSD1 inhibitors have been synthesized and biologically evaluated. These compounds exhibit excellent HSD1 potency and HSD2 selectivity and good pharmacokinetic and pharmacodynamic profiles. 相似文献
998.
Hydroxylated analogues of the orally active broad spectrum antifungal, Sch 51048 (1), and the discovery of posaconazole [Sch 56592; 2 or (S,S)-5 总被引:1,自引:0,他引:1
Bennett F Saksena AK Lovey RG Liu YT Patel NM Pinto P Pike R Jao E Girijavallabhan VM Ganguly AK Loebenberg D Wang H Cacciapuoti A Moss E Menzel F Hare RS Nomeir A 《Bioorganic & medicinal chemistry letters》2006,16(1):186-190
As part of a detailed study, the syntheses, biological activities, and pharmacokinetic properties of hydroxylated analogues of the previously described broad spectrum antifungal agents, Sch 51048 (1), Sch 50001 (3), and Sch 50002 (4), are described. Based on an overall superior profile, one of the alcohols, Sch 56592 (2), was selected for clinical studies. 相似文献
999.
Zheng GZ Bhatia P Kolasa T Patel M El Kouhen OF Chang R Uchic ME Miller L Baker S Lehto SG Honore P Wetter JM Marsh KC Moreland RB Brioni JD Stewart AO 《Bioorganic & medicinal chemistry letters》2006,16(18):4936-4940
We have discovered a novel, potent, and selective triazafluorenone series of metabotropic glutamate receptor 1 (mGluR1) antagonists with efficacy in various rat pain models. Pharmacokinetic and pharmacodynamic profiles of these triazafluorenone analogs revealed that brain/plasma ratios of these mGluR1 antagonists were important to achieve efficacy in neuropathic pain models. This correlation could be used to guide our in vivo SAR (structure-activity relationship) modification. For example, compound 4a has a brain/plasma ratio of 0.34, demonstrating only moderate efficacy in neuropathic pain models. On the other hand, antagonist 4b with a brain/plasma ratio of 2.70 was fully efficacious in neuropathic pain models. 相似文献
1000.
Hepcidin was originally identified as a liver-expressed antimicrobial peptide but further studies have shown that it also
has a key role in iron homeostasis. The NMR structure of the synthetic peptides reveal a distorted beta-sheet containing 4
disulphide bridges, with an unusual vicinal disulphide bridge which has been suggested to be functionally significant. In
this study, we report the presence of co-purified iron with the urine-purified 20 and 25 residue hepcidins. Since the published
structure does not allow metal binding, the interaction of hepcidin with metals was investigated for other possible structural
conformations by threading its primary sequence onto existing 3D folds. Several alignments were obtained and the best scores
were used to build a 3D model of hepcidin containing one atom of iron. The new 3D structure, that contains only reduced Cys
residues, is completely different from the solved structure of the synthetic peptide. Although the model presented here shows
only one metal bound to the peptide, the binding of several metal atoms cannot be excluded from such a short flexible peptide.
The co-purification of iron with both peptides, together with our 3D model, suggest a conformational polymorphism for hepcidin,
reminiscent of the iron regulatory proteins IRPs. 相似文献