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991.
Upul K. Bandarage Jingrong Cao Jon H. Come John J. Court Huai Gao Marc D. Jacobs Craig Marhefka Suganthi Nanthakumar Jeremy Green 《Bioorganic & medicinal chemistry letters》2018,28(15):2622-2626
Rho kinase (ROCK) inhibitors are potential therapeutic agents for the treatment of a variety of disorders including hypertension, glaucoma and erectile dysfunction. Here we disclose a series of potent and selective ROCK inhibitors based on a substituted 7-azaindole scaffold. Substitution of the 3-position of 7-azaindole led to compounds such as 37, which possess excellent ROCK inhibitory potency and high selectivity against the closely related kinase PKA. 相似文献
992.
Julia Perdrial Paul D. Brooks Tyson Swetnam Kathleen A. Lohse Craig Rasmussen Marcy Litvak Adrian A. Harpold Xavier Zapata-Rios Patrick Broxton Bhaskar Mitra Tom Meixner Kate Condon David Huckle Clare Stielstra Angélica Vázquez-Ortega Rebecca Lybrand Molly Holleran Caitlin Orem Jon Pelletier Jon Chorover 《Biogeochemistry》2018,138(3):225-243
Climate-driven changes in carbon (C) cycling of forested ecosystems have the potential to alter long-term C sequestration and the global C balance. Prior studies have shown that C uptake and partitioning in response to hydrologic variation are system specific, suggesting that a comprehensive assessment is required for distinct ecosystems. Many sub-humid montane forest ecosystems in the US are projected to experience increased water limitation over the next decades and existing water-limited forests can be used as a model for how changes in the hydrologic cycle will impact such ecosystems more broadly. Toward that goal we monitored precipitation, net ecosystem exchange and lateral soil and stream C fluxes in three semi-arid to sub-humid montane forest catchments for several years (WY 2009–2013) to investigate how the amount and timing of water delivery affect C stores and fluxes. The key control on aqueous and gaseous C fluxes was the distribution of water between winter and summer precipitation, affecting ecosystem C uptake versus heterotrophic respiration. We furthermore assessed C stores in soil and above- and below-ground biomass to assess how spatial patterns in water availability influence C stores. Topographically-driven patterns in catchment wetness correlated with modeled soil C stores, reflecting both long-term trends in local C uptake as well as lateral redistribution of C leached from upslope organic soil horizons to convergent landscape positions. The results suggest that changes in the seasonality of precipitation from winter snow to summer rain will influence both the amount and the spatial distribution of soil C stores. 相似文献
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996.
George Thom Jon Hatcher Arron Hearn Judy Paterson Natalia Rodrigo Arthur Beljean 《MABS-AUSTIN》2018,10(2):304-314
The blood-brain barrier (BBB) is a formidable obstacle for delivery of biologic therapeutics to central nervous system (CNS) targets. Whilst the BBB prevents passage of the vast majority of molecules, it also selectively transports a wide variety of molecules required to maintain brain homeostasis. Receptor-mediated transcytosis is one example of a macromolecule transport system that is employed by cells of the BBB to supply essential proteins to the brain and which can be utilized to deliver biologic payloads, such as antibodies, across the BBB. In this study, we performed phage display selections on the mouse brain endothelial cell line, bEND.3, to enrich for antibody single-chain variable fragments (scFvs) that could compete for binding with a known BBB-crossing antibody fragment, FC5. A number of these scFvs were converted to IgGs and characterized for their ability to bind to mouse, rat and human brain endothelial cells, and subsequent ability to transport across the BBB. We demonstrated that these newly identified BBB-targeting IgGs had increased brain exposure when delivered peripherally in mice and were also able to transport a biologically active molecule, interleukin-1 receptor antagonist (IL-1RA), into the CNS. The antagonism of the interleukin-1 system within the CNS can result in the relief of neuropathic pain. We demonstrated that the BBB-targeting IgGs were able to elicit an analgesic response in a mouse model of nerve ligation-induced hypersensitivity when fused to IL-1RA. 相似文献
997.
Alexander M. W. Cargill Thompson Jon A. McCleverty Michael D. Ward 《Inorganica chimica acta》1996,250(1-2):29-34
Two multinucleating ligands have been prepared from 1,3,5-tris(3,5-dibromophenyl)benzene by multiple Pd(0)-catalysed cross-coupling reactions. 1,3,5-Tris[3,5-bis(4-pyridylethenyl)phenyl]benzene (L1) has six remote pyridyl moieties, each of which can coordinate a 17 valence-electron Mo(tp*)(NO)Cl fragment (tp* = hydrotris(3,5-dimethylpyrazolyl)borate), affording the hexanuclear complex [Cl(NO)(tp*)Mo6(L1) (1). 1,3,5-Tris[3,5-bis(2-pyridyl)phenyl]benzene (L2) incorporates three potentially terdentate, cyclometallating N,C,N-donor sets, and can coordinate three Ru(tpy)2+ fragments (tpy = 2,2′:6′,2″-terpyridine) giving the trinuclear complex [(tpy)Ru3(L2)][PF6]3 (2). Complex 1 is EPR active, with nearest-neighbour pairs of molybdenum centres displaying magnetic exchange interactions. Electrochemical studies of the two complexes suggest that there is little ground-state interaction between the metal centres in either case. 相似文献
998.
The polymerase chain reaction (PCR) was used to amplify eubacterial small-subunit (16S) ribosomal DNA (rDNA) genes from galls of the marine red alga Prionitis lanceolata Harvey (Gigartinales). These tumors consist of hypertrophied algal cells containing large numbers of intercellular bacteria that remain uncultivable. PCR-amplified 16S rDNAs from surface-sterilized gall tissue plugs were cloned, sequenced, and analyzed by alignment to available small-subunit rRNA sequences (University of Illinois Ribosomal Database Project). Variable regions were identified and used to construct a fluorescently labeled, species-specific oligodeoxynucleotide probe for whole cell in situ hybridization to the gall symbiont. Probe 949 (PLANC.949) localized the P. lanceolata bacterial symbiont in preparations from mature gall tissue. This probe did not hybridize to the rDNA of closely related bacteria included as controls in the same hybridization reactions, In situ hybridization revealed the presence of the same bacterium in association with P. lanceolata gall formation from three central California localities. Distance and parsimony analyses suggest that this organism is a member of the Proteobacteria (alpha subdivision; Rhodobacter group) and is most closely related to Roseobacter denitrificans . 相似文献
999.
Krzysztof Szczyglowski Trevor Potter Jon Stoltzfus Susan Y. Fujimoto Frans J. de Bruijn 《Plant molecular biology》1996,31(4):931-935
The involvement of the Sesbania rostrata glb3 gene promoter NICE (nodule-infected cell expression) element in root-enhanced expression of 5-Srglb3-uidA-3nos chimeric gene was investigated in transgenic Nicotiana tabacum plants. The full-length wild-type Srglb3 promoter directed root meristem-enhanced expression in transgenic tobacco plants. The expression pattern of nine selected Srglb3 promoter mutations in the NICE element was examined in transgenic tobacco plants and compared with the pattern observed in nodules of transgenic Lotus corniculatus plants. The results suggest that the highly conserved motifs in the NICE element play an important role in expression in roots of non-legume plants. 相似文献
1000.
Thomas O Baldwin Jon A Christopher Frank M Raushel James F Sinclair Miriam M Ziegler Andrew J Fisher Ivan Rayment 《Current opinion in structural biology》1995,5(6)
The generation of light by living organisms such as fireflies, glow-worms, mushrooms, fish, or bacteria growing on decaying materials has been a subject of fascination throughout the ages, partly because it occurs without the need for high temperatures. The chemistry behind the numerous bioluminescent systems is quite varied, and the enzymes that catalyze the reactions, the luciferases, are a large and evolutionarily diverse group. The structure of the best understood of these intriguing enzymes, bacterial luciferase, has recently been determined, allowing discussion of features of the protein in structural terms for the first time. 相似文献