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991.
992.
993.
Abdala Hiam David Sebastien Bekesi George Fellous Arlette Jorge Kalil Patrice Le Pape 《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):305-312
A new family of antimicrotubule drugs named (3-haloacetamidobenzoyl) ureas and ethyl 3-haloacetamidobenzoates were found to be cytotoxic to the Leishmania parasite protozoa. While the benzoylureas were shown to strongly inhibit in vitro mammalian brain microtubule assembly, the ethyl ester derivatives were characterized as very poor inhibitors of this process. Ethyl 3-chloroacetamidobenzoate, MF29, was found to be the most efficient drug on the promastigote stage of three Leishmania species (IC50: 0.3–1.8 μM). MF29 maintained its activity against the clinical relevant intracellular stage of L. mexicana with IC50 value of 0.33 μM. It was the only compound that exhibits a high activity on all the Leishmania species tested. This compound appeared to alter parasite microtubule organisation as demonstrated by using antibodies directed against microtubule components and more precisely the class of microtubule decorated by the MAP2-like protein. It is interesting to notice that this MAP2-like protein was identified for the first time in a Leishmania parasite 相似文献
994.
Mansour Alsharidah Norman R. Lazarus Tomasz E. George Chibeza C. Agley Stephen D. R. Harridge 《Aging cell》2013,12(3):333-344
The myogenic behaviour of primary human muscle precursor cells (MPCs) obtained from young (aged 20–25 years) and elderly people (aged 67–82 years) was studied in culture. Cells were compared in terms of proliferation, DNA damage, time course and extent of myogenic marker expression during differentiation, fusion, size of the formed myotubes, secretion of the myogenic regulatory cytokine TGF‐β1 and sensitivity to TGF‐β1 treatment. No differences were observed between cells obtained from the young and elderly people. The cell populations were expanded in culture until replicative senescence. Cultures that maintained their initial proportion of myogenic cells (desmin positive) with passaging (n = 5) were studied and compared with cells from the same individuals in the non‐senescent state. The senescent cells exhibited a greater number of cells with DNA damage (γ‐H2AX positive), showed impaired expression of markers of differentiation, fused less well, formed smaller myotubes and secreted more TGF‐β. The data strongly suggest that MPCs from young and elderly people have similar myogenic behaviour. 相似文献
995.
Aamer Sandoo Neil Chanchlani James Hodson Jacqueline P Smith Karen M Douglas George D Kitas 《Arthritis research & therapy》2013,15(6):R203
Introduction
Patients with rheumatoid arthritis (RA) are at an increased risk for cardiovascular disease (CVD). An early manifestation of CVD is endothelial dysfunction which can lead to functional and morphological vascular abnormalities. Classical CVD risk factors and inflammation are both implicated in causing endothelial dysfunction in RA. The objective of the present study was to examine the effect of baseline inflammation, cumulative inflammation, and classical CVD risk factors on the vasculature following a six-year follow-up period.Methods
A total of 201 RA patients (155 females, median age (25th to 75th percentile): 61 years (53 to 67)) were examined at baseline (2006) for presence of classical CVD risk factors and determination of inflammation using C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). At follow-up (2012) patients underwent assessments of microvascular and macrovascular endothelium-dependent and endothelium-independent function, along with assessment of carotid atherosclerosis. The CRP and ESR were recorded from the baseline study visit to the follow-up visit for each patient to calculate cumulative inflammatory burden.Results
Classical CVD risk factors, but not RA disease-related inflammation, predicted microvascular endothelium-dependent and endothelium-independent function, macrovascular endothelium-independent function and carotid atherosclerosis. These findings were similar in a sub-group of patients free from CVD, and not receiving non-steroidal anti-inflammatory drugs, cyclooxygenase 2 inhibitors or biologics. Cumulative inflammation was not associated with microvascular and macrovascular endothelial function, but a weak association was apparent between area under the curve for CRP and carotid atherosclerosis.Conclusions
Classical CVD risk factors may be better long-term predictors of vascular function and morphology than systemic disease-related inflammation in patients with RA. Further studies are needed to confirm if assessments of vascular function and morphology are predictive of long-term CV outcomes in RA. 相似文献996.
Sebastian M. Marcuccio Bryan C. Elmes George Holan E. John Middleton 《Nucleosides, nucleotides & nucleic acids》2013,32(10):1695-1701
Abstract An economical two pot synthesis of 2′,3′-dideoxycytidine (2) from N4-acetyl-cytidine (4) has been developed. The key feature of this sequence is the in situ reductive elimination of a mixture of 1-(3-bromo-3-deoxy-2,5-di-O-acetyl-β-D-xylofuranosyl)-N4-acetylcytosine (5) and 1-(2-bromo-3-deoxy-3,5-di-O-acetyl-β-D-arabinofuranosyl)-N4-acetylcytosine (6) and subsequent hydrogenation of the resultant olefin over palladised charcoal. 相似文献
997.
Carston R. Wagner Shu-Ling Chang George W. Griesgraber Heng Song Edward J. McIntee Cheryl L. Zimmerman 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):913-919
Abstract Stable and water soluble amino acid phosphomonoester amidates of AZT were synthesized and shown to have potent anti-HIV-1 activity. Intracellular and cell extract metabolism studies revealed that these compounds are likely to be enzymatically converted to the corresponding monophosphates. In addition, we have shown that the half life and tissue distribution of a phosphoramidate of AZT is 5 and 10-fold greater, respectively, than AZT. 相似文献
998.
Robert Vince Mel Hua Jay Brownell George C. Lavelle Jeanine Qualls William M. Shannon 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):1127-1128
Abstract Carbocyclic 2′, 3′-didehydro-2′,3′-dideoxyquanosine (carbovir), a novel nucleoside analog, emerged as a potent and selective anti-HIV agent from a primary screen of a large number of carbocyclic nucleosides.1 Carbovir inhibited the infectivity and replication of HIV in T-cells at concentrations 200 to 400-fold below toxicity to host cells. Carbovir was also evaluated for its Inhibitory effects on the expression of viral antigen in HIV-infected CEM cells. Production of p 24 core antigen at optimal inhibitory concentrations of the antiviral agents indicated comparable results for AZT, ddA and carbovir. 相似文献
999.
Jean-Luc Girardet John C. Drach Stanley D. Chamberlain George W. KosLzalka Leroy B. Townsend 《Nucleosides, nucleotides & nucleic acids》2013,32(12):2389-2401
Abstract A number of 2-substituted-5,6-dichloro-l-(α-L-arabinofuranosyl)benzimidazoles have been prepared by condensation of 2-bromo-5,6-dichlorobenzimidazole or 2,5,6-trichlorobenzimidazole with tetra-O-acetyl-L-arabinofuranose. 2-Alkylamino derivatives were prepared by a substitution of the 2-chloro group with the appropriate amines. All target compounds were evaluated for activity against HCMV and HSV-1. The 2-chloro and 2-bromo derivatives showed moderate activity against HCMV at non-cytotoxic concentrations. 相似文献
1000.
George L. Trainor Frank W. Hobbs Anthony J. Cocuzza Pat N. Confalone 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):1175-1176
Abstract A general route for the synthesis of alkynylamino nucleoside triphosphates is described. These nucleosides can be selectively coupled through the alkynylamino group to a variety of reporter groups and used to enzymatically label DNA. 相似文献