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排序方式: 共有291条查询结果,搜索用时 46 毫秒
91.
Madsen-Duggan CB Debenham JS Walsh TF Toupence RB Huang SX Wang J Tong X Lao J Fong TM Schaeffer MT Xiao JC Huang CR Shen CP Stribling DS Shearman LP Strack AM MacIntyre DE Van der Ploeg LH Goulet MT 《Bioorganic & medicinal chemistry letters》2007,17(7):2031-2035
Optimization of the biological activity for 5,6-diarylpyridines as CB1 receptor inverse agonists is described. Food intake and pharmacokinetic evaluation of 3f and 15c indicate that these compounds are effective orally active modulators of CB1. 相似文献
92.
Armstrong HE Galka A Lin LS Lanza TJ Jewell JP Shah SK Guthikonda R Truong Q Chang LL Quaker G Colandrea VJ Tong X Wang J Xu S Fong TM Shen CP Lao J Chen J Shearman LP Stribling DS Rosko K Strack A Ha S Van der Ploeg L Goulet MT Hagmann WK 《Bioorganic & medicinal chemistry letters》2007,17(8):2184-2187
Sulfonamide analogues of the potent CB1R inverse agonist taranabant were prepared and optimized for potency and selectivity for CB1R. They were variably more potent than the corresponding amide analogues. The most potent representative 22 had good pharmacokinetic and brain levels, but was modestly active in blocking CB1R agonist-mediated hypothermia. 相似文献
93.
Wetlands Ecology and Management - Oil and gas exploration has resulted in over 300,000 km of linear disturbances, known as seismic lines, throughout boreal peatlands across Canada. Sites... 相似文献
94.
Zhu YF Wilcoxen K Gross T Connors P Strack N Gross R Huang CQ McCarthy JR Xie Q Ling N Chen C 《Bioorganic & medicinal chemistry letters》2003,13(11):1927-1930
A series of 1-benzoyl isoquinolines, based on compound 1, was synthesized and evaluated for their ability to displace IGF-I from its complex with IGF-binding protein-3. Successful modifications of 1 included the replacement of the 3,4-dihydroxybenzoyl group with a substituted benzyl group. These alternations culminated in the discovery of compounds such as 7o which had excellent in vitro potency (K(i)=9.4 nM) but with one less of the labile catechol functionality of 1. 相似文献
95.
Berger R Zhu C Hansen AR Harper B Chen Z Holt TG Hubert J Lee SJ Pan J Qian S Reitman ML Strack AM Weingarth DT Wolff M Macneil DJ Weber AE Edmondson SD 《Bioorganic & medicinal chemistry letters》2008,18(17):4833-4837
The discovery and structure–activity relationship of 1,2-diarylimidazole piperazine carboxamides bearing polar side chains as potent and selective cholecystokinin 1 receptor (CCK1R) agonists are described. Optimization of this series resulted in the discovery of isopropyl carboxamide 40, a CCK1R agonist with sub-nanomolar functional and binding activity as well as excellent potency in a mouse overnight food intake reduction assay. 相似文献
96.
Zhu C Hansen AR Bateman T Chen Z Holt TG Hubert JA Karanam BV Lee SJ Pan J Qian S Reddy VB Reitman ML Strack AM Tong V Weingarth DT Wolff MS MacNeil DJ Weber AE Duffy JL Edmondson SD 《Bioorganic & medicinal chemistry letters》2008,18(15):4393-4396
High-throughput screening revealed diaryl pyrazole 3 as a selective albeit modest cholecystokinin 1 receptor (CCK1R) agonist. SAR studies led to the discovery and optimization of a novel class of 1,2-diaryl imidazole carboxamides. Compound 44, which was profiled extensively, showed good in vivo mouse gallbladder emptying (mGBE) and lean mouse overnight food intake (ONFI) reduction activities. 相似文献
97.
Analysis of the catalytic properties of the serine carboxypeptidase-like (SCPL) 1-O-sinapoyl-beta-glucose:l-malate sinapoyltransferase (SMT) from Arabidopsis showed that the enzyme exhibits besides its primary sinapoylation of l-malate, minor hydrolytic and disproportionation activities, producing free sinapic acid and 1,2-di-O-sinapoyl-beta-glucose, respectively. The ability of the enzyme to liberate sinapic acid from the donor molecule 1-O-sinapoyl-beta-glucose indicates the existence of a short-lived acylenzyme intermediate in the proposed random sequential bi-bi mechanism of catalysis. SMT-catalyzed formation of disinapoylglucose has been corroborated by docking studies with an established homology structure model that illustrates the possible binding of two 1-O-sinapoyl-beta-glucose molecules in the active site and the intermolecular reaction of the two glucose esters. The SMT gene is embedded in a tandem cluster of five SCPL sinapoyltransferase genes, which encode enzymes with high amino acid sequence identities and partially overlapping substrate specificities. We assume that in recent duplications of genes encoding SCPL proteins, neofunctionalization of the duplicates to accept 1-O-sinapoyl-beta-glucose as acyl donor was gained first, followed by subfunctionalization leading to different acyl acceptor specificities. 相似文献
98.
Sun Z Hans J Walter MH Matusova R Beekwilder J Verstappen FW Ming Z van Echtelt E Strack D Bisseling T Bouwmeester HJ 《Planta》2008,228(5):789-801
99.
Kimberley R. Murray Andrea K. Borkenhagen David J. Cooper Maria Strack 《Wetlands Ecology and Management》2017,25(4):501-515
The moss layer transfer technique removes the top layer of vegetation from donor sites as a method to transfer propagules and restore degraded or reclaimed peatlands. As this technique is new, little is known about the impacts of moss layer transfer on vegetation and carbon fluxes following harvest. We monitored growing season carbon dioxide (CO2) and methane (CH4) fluxes as well as plant communities at donor sites and neighbouring natural peatland sites in an ombrotrophic bog and minerotrophic fen in Alberta, Canada from which material was harvested between 1 and 6 years prior to the study. Plant recovery at all donor sites was rapid with an average of 72% total plant cover one growing season after harvest at the fen and an average of 87% total plant cover two growing seasons after harvest at the bog. Moss cover also returned, averaging 84% 6 years after harvest at the bog. The majority of natural peatlands in western Canada are treed and tree recruitment at the donor sites was limited. Methane emissions were higher from donor sites compared to natural sites due to the high water table and greater sedge cover. Carbon budgets suggested that the donor fen and bog sites released higher CO2 and CH4 over the growing season compared to adjacent natural sites. However, vegetation re-establishment on donor sites was rapid, and it is possible that these sites will return to their original carbon-cycle functioning after disturbance, suggesting that donor sites may recover naturally without implementing management strategies. 相似文献
100.
Martin Strack Étienne Billard David Chatenet William D. Lubell 《Bioorganic & medicinal chemistry letters》2017,27(15):3412-3416
A novel approach for the synthesis of head-to-tail cyclic peptides has been developed and used to prepare two mimics of the urotensin II-related peptide (URP) cyclic core. Mimics 1 and 2 (c[Trp-Lys-Tyr-Gly-ψ(triazole)-Gly] and c[Phe-Trp-Lys-Tyr-Gly-ψ(triazole)-Gly]) were respectively prepared using a combination of solid- and solution-phase synthesis. The silyl-based alkyne-modifying (SAM) linker enabled installation of C-terminal alkyne and N-terminal azide moieties onto linear peptide precursors, which underwent head-to-tail copper-catalyzed azide-alkyne cycloaddition (CuAAC) in solution. In an aortic ring contraction assay, neither 1 nor 2 exhibited agonist activity; however, both inhibited selectively URP- but not UII-mediated vasoconstriction. The core phenylalanine residue was shown to be important for enhancing modulatory activity of the urotensinergic system. 相似文献