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991.
Will Fischer Cristian Apetrei Mario L. Santiago Yingying Li Rajeev Gautam Ivona Pandrea George M. Shaw Beatrice H. Hahn Norman L. Letvin Gary J. Nabel Bette T. Korber 《Journal of virology》2012,86(24):13217-13231
Simian immunodeficiency virus (SIV) infection of rhesus macaques causes immune depletion and disease closely resembling human AIDS and is well recognized as the most relevant animal model for the human disease. Experimental investigations of viral pathogenesis and vaccine protection primarily involve a limited set of related viruses originating in sooty mangabeys (SIVsmm). The diversity of human immunodeficiency virus type 1 (HIV-1) has evolved in humans in about a century; in contrast, SIV isolates used in the macaque model evolved in sooty mangabeys over millennia. To investigate the possible consequences of such different evolutionary histories for selection pressures and observed diversity in SIVsmm and HIV-1, we isolated, sequenced, and analyzed 20 independent isolates of SIVsmm, including representatives of 7 distinct clades of viruses isolated from natural infection. We found SIVsmm diversity to be lower overall than HIV-1 M group diversity. Reduced positive selection (i.e., less diversifying evolution) was evident in extended regions of SIVsmm proteins, most notably in Gag p27 and Env gp120. In addition, the relative diversities of proteins in the two lineages were distinct: SIVsmm Env and Gag were much less diverse than their HIV-1 counterparts. This may be explained by lower SIV-directed immune activity in mangabeys relative to HIV-1-directed immunity in humans. These findings add an additional layer of complexity to the interpretation and, potentially, to the predictive utility of the SIV/macaque model, and they highlight the unique features of human and simian lentiviral evolution that inform studies of pathogenesis and strategies for AIDS vaccine design. 相似文献
992.
What implications might synthetic biology’s potential as a wholly new method of production have for the world economy, particularly developing countries? Theories of political economy predict that synthetic biology can shift terms of trade and displace producers in developing countries. Governments, however, retain the ability to mitigate negative changes through social safety nets and to foster adaptation to some changes through research, education and investment. We consider the effects the synthetic production of otherwise naturally derived molecules are likely to have on trade and investment, particularly in developing countries. Both rubber in Malaysia and indigo dyes in India provide historical examples of natural molecules that faced market dislocations from synthetic competitors. Natural rubber was able to maintain significant market share, while natural indigo vanished from world markets. These cases demonstrate the two extremes of the impact synthetic biology might have on naturally derived products. If developing countries can cushion the pain of technological changes by providing producers support as they retool or exit, the harmful effects of synthetic biology can be mitigated while its benefits can still be captured. 相似文献
993.
Chen HC Bandyopadhyay G Sajan MP Kanoh Y Standaert M Farese RV Farese RV 《The Journal of biological chemistry》2002,277(26):23554-23562
Exercise increases glucose transport in muscle by activating 5'-AMP-activated protein kinase (AMPK), but subsequent events are unclear. Presently, we examined the possibility that AMPK increases glucose transport through atypical protein kinase Cs (aPKCs) by activating proline-rich tyrosine kinase-2 (PYK2), ERK pathway components, and phospholipase D (PLD). In mice, treadmill exercise rapidly activated ERK and aPKCs in mouse vastus lateralis muscles. In rat extensor digitorum longus (EDL) muscles, (a) AMPK activator, 5-aminoimidazole-4-carboxamide-1-beta-d-riboside (AICAR), activated PYK2, ERK and aPKCs; (b) effects of AICAR on ERK and aPKCs were blocked by tyrosine kinase inhibitor, genistein, and MEK1 inhibitor, PD98059; and (c) effects of AICAR on aPKCs and 2-deoxyglucose (2-DOG) uptake were inhibited by genistein, PD98059, and PLD-inhibitor, 1-butanol. Similarly, in L6 myotubes, (a) AICAR activated PYK2, ERK, PLD, and aPKCs; (b) effects of AICAR on ERK were inhibited by genistein, PD98059, and expression of dominant-negative PYK2; (c) effects of AICAR on PLD were inhibited by MEK1 inhibitor UO126; (d) effects of AICAR on aPKCs were inhibited by genistein, PD98059, 1-butanol, and expression of dominant-negative forms of PYK2, GRB2, SOS, RAS, RAF, and ERK; and (e) effects of AICAR on 2DOG uptake/GLUT4 translocation were inhibited by genistein, PD98059, UO126, 1-butanol, cell-permeable myristoylated PKC-zeta pseudosubstrate, and expression of kinase-inactive RAF, ERK, and PKC-zeta. AMPK activator dinitrophenol had effects on ERK, aPKCs, and 2-DOG uptake similar to those of AICAR. Our findings suggest that effects of exercise on glucose transport that are dependent on AMPK are mediated via PYK2, the ERK pathway, PLD, and aPKCs. 相似文献
994.
Kobza KA Chaiseeda K Sarath G Takacs JM Zempleni J 《The Journal of nutritional biochemistry》2008,19(12):826-832
Posttranslational modification of histones by biotinylation can be catalyzed by both biotinidase (BTD) and holocarboxylase synthetase. Biotinylation of histones is an important epigenetic mechanism to regulate gene expression, DNA repair, and chromatin remodeling. The role of BTD in histone biotinylation is somewhat ambiguous, given that BTD also catalyzes removal of the biotin tag from histones. Here, we sought to develop BTD inhibitors for future studies of the role of BTD in altering chromatin structure. We adopted an existing colorimetric BTD assay for use in a novel 96-well plate format to permit high-throughput screening of potential inhibitors. Biotin analogs were chemically synthesized and tested for their ability to inhibit human BTD. Seven of these compounds inhibited BTD by 26–80%. Biotinyl-methyl 4-(amidomethyl)benzoate had the largest effect on BTD, causing an 80% inhibition at 1 mM concentration. Enzyme kinetics studies were conducted to determine Vmax, Km and Ki for the seven inhibitors; kinetics were consistent with the hypothesis that biotinyl-methyl 4-(amidomethyl)benzoate and the other compounds acted by competitive inhibition of BTD. Finally, biotinyl-methyl 4-(amidomethyl)benzoate did not affect biotin transport in human cells, suggesting specificity in regard to biotin-related processes. 相似文献
995.
Das G Thotala DK Kapoor S Karunanithi S Thakur SS Singh NS Varshney U 《The EMBO journal》2008,27(6):840-851
Translation initiation from the ribosomal P-site is the specialty of the initiator tRNAs (tRNA(fMet)). Presence of the three consecutive G-C base pairs (G29-C41, G30-C40 and G31-C39) in their anticodon stems, a highly conserved feature of the initiator tRNAs across the three kingdoms of life, has been implicated in their preferential binding to the P-site. How this feature is exploited by ribosomes has remained unclear. Using a genetic screen, we have isolated an Escherichia coli strain, carrying a G122D mutation in folD, which allows initiation with the tRNA(fMet) containing mutations in one, two or all the three G-C base pairs. The strain shows a severe deficiency of methionine and S-adenosylmethionine, and lacks nucleoside methylations in rRNA. Targeted mutations in the methyltransferase genes have revealed a connection between the rRNA modifications and the fundamental process of the initiator tRNA selection by the ribosome. 相似文献
996.
Enoyl-CoA hydratase. reaction,mechanism, and inhibition 总被引:3,自引:0,他引:3
Enoyl-CoA hydratase (ECH) catalyzes the second step in the physiologically important beta-oxidation pathway of fatty acid metabolism. This enzyme facilitates the syn-addition of a water molecule across the double bond of a trans-2-enoyl-CoA thioester, resulting in the formation of a beta-hydroxyacyl-CoA thioester. The catalytic mechanism of this proficient enzyme has been studied in great depth through a combination of kinetic, spectroscopic, and structural techniques, and is proposed to occur via the formation of a single transition state. Sequence alignment and mutagenesis studies have implicated the key residues important for catalysis: Gly-141, Glu-144, and Glu-164 (rat liver ECH numbering). The two catalytic glutamic acid residues are believed to act in concert to activate a water molecule, while Gly-141 is proposed to be involved in substrate activation. Recently, two potent inhibitors of ECH have been reported in the literature, which result in the irreversible inactivation of the enzyme via covalent adduct formation. This review summarizes studies on the structure, mechanism, and inhibition of ECH. 相似文献
997.
Due to hostile condition of red mud (RM), its utilization for vegetation is restricted. Therefore, RM with biowastes as soil amendment may offer suitable combination to support plant growth with reduced risk of metal toxicity. To evaluate the effects of RM on soil properties, plant growth performance, and metal accumulation in lemongrass, a study was conducted using different RM concentrations (0, 5, 10, and 15% w/w) in soil amended with biowastes [cow dung manure (CD) or sewage-sludge (SS)]. Application of RM in soil with biowastes improved organic matter and nutrient contents and caused reduction in phytoavailable metal contents. Total plant biomass was increased under all treatments, maximally at 5% RM in soil with SS (91.4%) and CD (51.7%) compared to that in control (no RM and biowastes). Lemongrass acted as a potential metal-tolerant plant as its metal tolerance index is >100%. Based on translocation and bioconcentration factors, lemongrass acted as a potential phytostabilizer of Fe, Mn, and Cu in roots and was found efficient in translocation of Al, Zn, Cd, Pb, Cr, As, and Ni from roots to shoot. The study suggests that 5% RM with biowastes preferably SS may be used to enhance phytoremediation potential of lemongrass. 相似文献
998.
999.
Resting state networks (RSNs) have been studied extensively with functional MRI in humans in health and disease to reflect brain function in the un-stimulated state as well as reveal how the brain is altered with disease. Rodent models of disease have been used comprehensively to understand the biology of the disease as well as in the development of new therapies. RSN reported studies in rodents, however, are few, and most studies are performed with anesthetized rodents that might alter networks and differ from their non-anesthetized state. Acquiring RSN data in the awake rodent avoids the issues of anesthesia effects on brain function. Using high field fMRI we determined RSNs in awake rats using an independent component analysis (ICA) approach, however, ICA analysis can produce a large number of components, some with biological relevance (networks). We further have applied a novel method to determine networks that are robust and reproducible among all the components found with ICA. This analysis indicates that 7 networks are robust and reproducible in the rat and their putative role is discussed. 相似文献
1000.