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941.
Zenas George Yusuf Omosun Anthony A. Azenabor Jason Goldstein James Partin Kahaliah Joseph Debra Ellerson Qing He Francis Eko Melissa A. McDonald Matthew Reed Pavel Svoboda Olga Stuchlik Jan Pohl Erika Lutter Claudiu Bandea Carolyn M. Black Joseph U. Igietseme 《Biochemical and biophysical research communications》2019,508(2):421-429
The unfolded protein response (UPR) contributes to chlamydial pathogenesis, as a source of lipids and ATP during replication, and for establishing the initial anti-apoptotic state of host cell that ensures successful inclusion development. The molecular mechanism(s) of UPR induction by Chlamydia is unknown. Chlamydia use type III secretion system (T3SS) effector proteins (e.g, the Translocated Actin-Recruiting Phosphoprotein (Tarp) to stimulate host cell's cytoskeletal reorganization that facilitates invasion and inclusion development. We investigated the hypothesis that T3SS effector-mediated assembly of myosin-II complex produces activated non-muscle myosin heavy chain II (NMMHC-II), which then binds the UPR master regulator (BiP) and/or transducers to induce UPR. Our results revealed the interaction of the chlamydial effector proteins (CT228 and Tarp) with components of the myosin II complex and UPR regulator and transducer during infection. These interactions caused the activation and binding of NMMHC-II to BiP and IRE1α leading to UPR induction. In addition, specific inhibitors of myosin light chain kinase, Tarp oligomerization and myosin ATPase significantly reduced UPR activation and Chlamydia replication. Thus, Chlamydia induce UPR through T3SS effector-mediated activation of NMMHC-II components of the myosin complex to facilitate infectivity. The finding provides greater insights into chlamydial pathogenesis with the potential to identify therapeutic targets and formulations. 相似文献
942.
Economic Botany - Dioscorea hirtiflora Benth. is an indigenous wild edible tuberous climbing plant native to Zambia. Known as lusala, the tubers are sold in markets across southern Zambia. Lusala... 相似文献
943.
Douglas Rodríguez‐Olarte Donald C. Taphorn Henry Agudelo‐Zamora 《Zeitschrift fur angewandte Ichthyologie》2019,35(2):600-604
This report describes the length–weight relationships (LWRs) of 22 freshwater fish species from freshwater western Caribbean drainages in Venezuela. Fishes were collected in dry seasons between 2005 and 2007 with standardized electrofishing from coastal streams of Aroa, Yaracuy and Urama drainages. Results include the first LWR information for ten endemic and threatened species. Novel data on these freshwater fish faunas are important for monitoring their populations, as well as the condition of fluvial habitats to promote strategies for their conservation. 相似文献
944.
945.
Dhaval P. Bhatt C. Allie Mills Kristin A. Anderson Brbara J. Henriques Tnia G. Lucas Sara Francisco Juan Liu Olga R. Ilkayeva Alexander E. Adams Shreyas R. Kulkarni Donald S. Backos Michael B. Major Paul A. Grimsrud Cludio M. Gomes Matthew D. Hirschey 《The Journal of biological chemistry》2022,298(4)
A wide range of protein acyl modifications has been identified on enzymes across various metabolic processes; however, the impact of these modifications remains poorly understood. Protein glutarylation is a recently identified modification that can be nonenzymatically driven by glutaryl-CoA. In mammalian systems, this unique metabolite is only produced in the lysine and tryptophan oxidative pathways. To better understand the biology of protein glutarylation, we studied the relationship between enzymes within the lysine/tryptophan catabolic pathways, protein glutarylation, and regulation by the deglutarylating enzyme sirtuin 5 (SIRT5). Here, we identify glutarylation on the lysine oxidation pathway enzyme glutaryl-CoA dehydrogenase (GCDH) and show increased GCDH glutarylation when glutaryl-CoA production is stimulated by lysine catabolism. Our data reveal that glutarylation of GCDH impacts its function, ultimately decreasing lysine oxidation. We also demonstrate the ability of SIRT5 to deglutarylate GCDH, restoring its enzymatic activity. Finally, metabolomic and bioinformatic analyses indicate an expanded role for SIRT5 in regulating amino acid metabolism. Together, these data support a feedback loop model within the lysine/tryptophan oxidation pathway in which glutaryl-CoA is produced, in turn inhibiting GCDH function via glutaryl modification of GCDH lysine residues and can be relieved by SIRT5 deacylation activity. 相似文献
946.
947.
948.
Andreea A. Gheorghita Francis Wolfram Gregory B. Whitfield Holly M. Jacobs Roland Pfoh Steven S.Y. Wong Allison K. Guitor Mara C. Goodyear Alison M. Berezuk Cezar M. Khursigara Matthew R. Parsek P. Lynne Howell 《The Journal of biological chemistry》2022,298(2)
Pseudomonas aeruginosa is an opportunistic human pathogen and a leading cause of chronic infection in the lungs of individuals with cystic fibrosis. After colonization, P. aeruginosa often undergoes a phenotypic conversion to mucoidy, characterized by overproduction of the alginate exopolysaccharide. This conversion is correlated with poorer patient prognoses. The majority of genes required for alginate synthesis, including the alginate lyase, algL, are located in a single operon. Previous investigations of AlgL have resulted in several divergent hypotheses regarding the protein’s role in alginate production. To address these discrepancies, we determined the structure of AlgL and, using multiple sequence alignments, identified key active site residues involved in alginate binding and catalysis. In vitro enzymatic analysis of active site mutants highlights R249 and Y256 as key residues required for alginate lyase activity. In a genetically engineered P. aeruginosa strain where alginate biosynthesis is under arabinose control, we found that AlgL is required for cell viability and maintaining membrane integrity during alginate production. We demonstrate that AlgL functions as a homeostasis enzyme to clear the periplasmic space of accumulated polymer. Constitutive expression of the AlgU/T sigma factor mitigates the effects of an algL deletion during alginate production, suggesting that an AlgU/T-regulated protein or proteins can compensate for an algL deletion. Together, our study demonstrates the role of AlgL in alginate biosynthesis, explains the discrepancies observed previously across other P. aeruginosa ΔalgL genetic backgrounds, and clarifies the existing divergent data regarding the function of AlgL as an alginate degrading enzyme. 相似文献
949.
Bradley D. Tait John Domagala Edmund L. Ellsworth Donna Ferguson Christopher Gajda Donald Hupe Elizabeth A. Lunney Peter J. Tummino 《Journal of molecular recognition : JMR》1996,9(2):139-142
New templates were designed and prepared which straddle the active site of HIV-1 protease. These templates were designed to be ‘flexible scaffolds’ upon which substituents could be appended to fill the pockets of HIV protease. The new templates prepared and analysed were 4-hydroxy-5H-furan-2-ones, 4-hydroxy-5,6-dihydropyrones, 3-hydroxy-cyclohex-2-enones, and 4-hydroxy-2(1H)-pyridinones, of which the 4-hydroxy- 5,6-dihydropyrones were found to be the most potent inhibitors of HIV-1 protease. 相似文献
950.