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121.
Ng VL; Hurt MH; Fein CL; Khayam-Bashi F; Marsh J; Nunes WM; McPhaul LW; Feigal E; Nelson P; Herndier BG 《Blood》1994,83(4):1067-1078
Two B-cell lines, 2F7 and 10C9, were established by single cell cloning from biopsies obtained from two acquired immune deficiency syndrome patients with Burkitt's lymphoma. Representation of the original tumors was verified by demonstration of (1) identical biallelic rearrangement of Ig genes for 2F7 and (2) shared idiotype for 10C9. Both cell lines displayed cell-surface Ig and secreted Ig (IgM lambda for 2F7, IgM kappa for 10C9). IgMs from both cell lines immunoprecipitated actin; in addition, 2F7 IgM lambda immunoprecipitated recombinant human immunodeficiency virus type 1 (HIV-1) gp 160. 2F7 IgM lambda did not react with other autoantigens (double-stranded and single-stranded DNA, actin, bovine serum albumin, IgG), whereas 10C9 IgM kappa reacted with human IgG. The 2F7 IgM heavy-chain variable region (VH) showed a 95% nucleotide homology with a previously sequenced VHIII germline gene, hv3019b9, whereas the 10C9 IgM VH showed a 95% homology with a previously sequenced VHIV germline gene, VH4.21. Use of minimally modified VH genes and demonstration of reactivity with chronically present antigens (ie, actin, HIV-1 gp 160, or human IgG) suggests that B cells in HIV-1-infected individuals proliferating in response to chronic antigenic stimulation may be at increased risk for lymphomagenesis. 相似文献
122.
F J Pearce J Forster G DeLeeuw J R Williamson G F Tutwiler 《Journal of molecular and cellular cardiology》1979,11(9):893-915
Studies with a new fatty acid oxidation inhibitor, 2-tetradecylglycidic acid, showed that half-maximal inhibition of oleate oxidation occurred at concentrations of 3 × 10−6m. 2-Tetradecylglycidic acid also inhibited endogenous fatty acid oxidation, but had little effect on octanoate oxidation. The inhibition of long chain fatty acid oxidation produced by 2-tetradecylglycidic acid depended on its time exposure to the hearts. At low work loads it had no effect on left ventricular pressure development or aortic output, but was inhibitory at high work loads when the capacity for glucose oxidation was exceeded.The relationship of oleate concentration (with 2% albumin present) to pyridine nucleotide fluorescence and to the stimulation of oxygen consumption was examined using hearts perfused with glucose. Pyridine nucleotide fluorescence and oxygen consumption were both increased, with half-maximal effects occurring at 0.08 mm and 0.2 mm oleate, respectively. Oleate addition, both in the absence and presence of insulin, increased oxygen consumption to a greater degree than expected from the theoretical decrease of the ratio associated with fatty acid oxidation. At fatty acid/albumin molar ratios of 2.5 or greater, contractility was impaired and oxygen consumption increased even further. Pyridine nucleotides remained reduced indicating the absence of an uncoupling effect on oxidative phosphorylation. The oxygen wasting effect of fatty acids is interpreted as caused by long chain fatty acyl-CoA formation and hydrolysis.In working heart preparations made hypoxic by lowering the perfusate oxygen content to about 35%, addition of 1 mm oleate to the perfusate resulted in a reversible decrease in left ventricular pressure development and aortic output. Perfusion with 5 × 10−5m 2-tetradecylglycidic acid for 40 min before oleate addition prevented this deleterious effect of oleate during hypoxia. Photographs of the surface pyridine nucleotide fluorescence showed that addition of oleate to the hypoxic heart resulted in an increase in the size and number of anoxic areas. Subsequent addition of 10−5m 2-tetradecylglycidic acid caused the anoxic areas to disappear. These results indicate that the deleterious effects of fatty acids on the hypoxic myocardium are due to an increased oxygen demand resulting from accelerated fatty acid oxidation. 相似文献
123.
Catherine E. Gleason Gustavo Frindt Chih-Jen Cheng Michael Ng Atif Kidwai Florian Lang Michel Baum Lawrence G. Palmer David Pearce Priyanka Rashmi 《The Journal of clinical investigation》2015,125(1):117-128
The epithelial Na+ channel (ENaC) is essential for Na+ homeostasis, and dysregulation of this channel underlies many forms of hypertension. Recent studies suggest that mTOR regulates phosphorylation and activation of serum/glucocorticoid regulated kinase 1 (SGK1), which is known to inhibit ENaC internalization and degradation; however, it is not clear whether mTOR contributes to the regulation of renal tubule ion transport. Here, we evaluated the effect of selective mTOR inhibitors on kidney tubule Na+ and K+ transport in WT and Sgk1–/– mice, as well as in isolated collecting tubules. We found that 2 structurally distinct competitive inhibitors (PP242 and AZD8055), both of which prevent all mTOR-dependent phosphorylation, including that of SGK1, caused substantial natriuresis, but not kaliuresis, in WT mice, which indicates that mTOR preferentially influences ENaC function. PP242 also substantially inhibited Na+ currents in isolated perfused cortical collecting tubules. Accordingly, patch clamp studies on cortical tubule apical membranes revealed that mTOR inhibition markedly reduces ENaC activity, but does not alter activity of K+ inwardly rectifying channels (ROMK channels). Together, these results demonstrate that mTOR regulates kidney tubule ion handling and suggest that mTOR regulates Na+ homeostasis through SGK1-dependent modulation of ENaC activity. 相似文献
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Mice are a widely utilized in vivo model for translational salivary gland research but must be used with caution. Specifically, mouse salivary glands are similar in many ways to human salivary glands (i.e., in terms of their anatomy, histology, and physiology) and are both readily available and relatively easy and affordable to maintain. However, there are some significant differences between the two organisms, and by extension, the salivary glands derived from them must be taken into account for translational studies. The current review details pertinent similarities and differences between human and mouse salivary glands and offers practical guidelines for using both for research purposes. 相似文献
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