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101.
Duarte CD Tributino JL Lacerda DI Martins MV Alexandre-Moreira MS Dutra F Bechara EJ De-Paula FS Goulart MO Ferreira J Calixto JB Nunes MP Bertho AL Miranda AL Barreiro EJ Fraga CA 《Bioorganic & medicinal chemistry》2007,15(6):2421-2433
We describe herein the discovery of LASSBio-881 (3c) as a novel in vivo antinociceptive, anti-inflammatory, and in vitro antiproliferative and antioxidant compound, with a cannabinoid ligand profile. We observed that LASSBio-881 (3c) was able to bind to CB1 receptors (71% at 100microM) and also to inhibit T-cell proliferation (66% at 10microM) probably by binding to CB2 receptors, in a non-proapoptotic manner, different from anandamide (1). It was also demonstrated that LASSBio-881 (3c) had an important antioxidant profile toward free radicals (DPPH and hydroxyl), probably due to its particular redox behavior, which reflects the presence of both nitro and 3,5-di-tert-butyl-4-hydroxyphenyl sub-units, as demonstrated by cyclic voltammetry studies. In addition, we showed that these structural sub-units are essential for the observed pharmacological activity. 相似文献
102.
Di Fabio R Alvaro G Bertani B Donati D Pizzi DM Gentile G Pentassuglia G Giacobbe S Spada S Ratti E Corsi M Quartaroli M Barnaby RJ Vitulli G 《Bioorganic & medicinal chemistry letters》2007,17(5):1176-1180
Chiral tetrahydroquinoline derivatives have been prepared by an asymmetric Mannich-type condensation reaction using commercially available vinyloxyethylsilane and a N-arylimino R-(+)-t-butyl lactate ester, in the presence of a catalytic amount of metal triflates as Lewis acids. This synthetic approach gave rise to the target aldehyde intermediate in moderate facial diastereoselectivity and in high chemical yield. This efficient route enabled to scale up the synthesis of an orally bioavailable glycine antagonist showing outstanding in vivo anti-hyperalgesic activity in different animal models of sustained inflammation and chronic neuropathic pain. 相似文献
103.
We have demonstrated the accuracy of a spatial stochastic model of Escherichia coli central carbon metabolism using the next subvolume method (NSM), an efficient implementation of the Gillespie direct method of stochastic simulation. Using this model, we demonstrate that compartmentalization of the enzymes comprising an engineered pathway for biosynthesis of R-1,2-propanediol leads to improved kinetic properties for the pathway enzymes, especially when substrate diffusivities are low. Our results suggest that enzyme compartmentalization is a powerful approach for improving the catalytic turnover of a channeled carbon substrate and should be particularly useful when applied to synthetic metabolic pathways that suffer from poor translation efficiency, are present in highly variable copy numbers, and have low turnover for new substrates. Furthermore, this approach represents a generic modeling framework for simultaneously analyzing spatial and stochastic events in cellular metabolism and should enable quantitative evaluation of the effect of enzyme compartmentalization on virtually any recombinant pathway. 相似文献
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105.
Stefania Neiva Lavorato Policarpo Ademar Sales Júnior Silvane Maria Fonseca Murta Alvaro José Romanha Ricardo José Alves/ 《Memórias do Instituto Oswaldo Cruz》2015,110(4):566-568
We describe herein the antitrypanosomal activity of 20 novel
1,3-bis(aryloxy)propan-2-amine derivatives. Compounds 2, 4, 6, 12, 15, 16 and 19 were
significantly active against amastigote and trypomastigote forms, with half maximal
inhibitory concentrationvalues in the range of 6-18 µM. In the cytotoxicity tests
against L929 cells, only compound 4 presented selectivity index value above 10,
indicating low toxicity. 相似文献
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108.
Yanping Geng Alexej Kedrov Joseph J. Caumanns Alvaro H. Crevenna Don C. Lamb Roland Beckmann Arnold J. M. Driessen 《The Journal of biological chemistry》2015,290(28):17250-17261
Members of the YidC/Oxa1/Alb3 protein family mediate membrane protein insertion, and this process is initiated by the assembly of YidC·ribosome nascent chain complexes at the inner leaflet of the lipid bilayer. The positively charged C terminus of Escherichia coli YidC plays a significant role in ribosome binding but is not the sole determinant because deletion does not completely abrogate ribosome binding. The positively charged cytosolic loops C1 and C2 of YidC may provide additional docking sites. We performed systematic sequential deletions within these cytosolic domains and studied their effect on the YidC insertase activity and interaction with translation-stalled (programmed) ribosome. Deletions within loop C1 strongly affected the activity of YidC in vivo but did not influence ribosome binding or substrate insertion, whereas loop C2 appeared to be involved in ribosome binding. Combining the latter deletion with the removal of the C terminus of YidC abolished YidC-mediated insertion. We propose that these two regions play an crucial role in the formation and stabilization of an active YidC·ribosome nascent chain complex, allowing for co-translational membrane insertion, whereas loop C1 may be involved in the downstream chaperone activity of YidC or in other protein-protein interactions. 相似文献
109.