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Shalini Mohan Nuzhat A. Kaushal A. Misra Deep C. Kaushal J. C. Katiyar S. Ghatak 《Immunological investigations》1988,17(4):295-307
The protein and antigenic composition of adult and larval stages of Ancylostoma ceylanicum, a human hookworm maintained in golden hamsters (Mesocricetus auratus), was studied employing immunochemical techniques. SDS-polyacrylamide gel electrophoresis revealed the presence of 47 and 43 protein bands in adult worms and infective larvae respectively in the molecular weight range of 10-170 kD. Crossed immunoelectrophoretic analysis, using immune rabbit sera, showed the presence of 32 antigenic peaks in adults and 19 in infective larval stage. Most of the antigens were common between adult and larval stage as evidenced by cross-line immunoelectrophoresis, although some stage specific antigens were also identified. These studies also demonstrate the complex nature of adult worms as compared to larvae. 相似文献
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Trushina E Singh RD Dyer RB Cao S Shah VH Parton RG Pagano RE McMurray CT 《Human molecular genetics》2006,15(24):3578-3591
We show that the mutant Huntington's disease (HD) protein (mhtt) specifically inhibits endocytosis in primary striatal neurons. Unexpectedly, mhtt does not inhibit clathrin-dependent endocytosis as was anticipated based on known interacting partners. Instead, inhibition occurs through a non-clathrin, caveolar-related pathway. Expression of mhtt inhibited internalization of BODIPY-lactosylceramide (LacCer), which is internalized by a caveolar-related mechanism. In contrast, endocytosis of Alexa Fluor 594-transferrin (Tfn) and epidermal growth factor, internalized through clathrin pathway, was unaffected by mhtt expression. Caveolin-1 (cav1), the major structural protein of caveolae binds cholesterol and is responsible for its trafficking inside cells. Mhtt interacts with cav-1 and caused a striking accumulation of intracellular cholesterol. Cholesterol accumulated in cultured neurons expressing mhtt in vitro and in brains of mhtt-expressing animals in vivo, and was observed after induction of mhtt expression in PC-12 cell lines. The accumulation occurred only when mhtt and cav1 were simultaneously expressed in cells. Knockdown of cav1 in mhtt-expressing neurons blocked cholesterol accumulation and restored LacCer endocytosis. Thus, mhtt and cav1 functionally interact to cause both cellular defects. These data provide the first direct link between mhtt and caveolar-related endocytosis and also suggest a possible mechanism for HD neurotoxicity where cholesterol homeostasis is perturbed. 相似文献
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The objectives of the present review is to update readers with the rapidly changing concepts in liver stem cell biology and related clinical applications. The liver has adapted to the inflow of ingested toxins by the evolutionary development of unique regenerative properties and responds to injury or tissue loss by rapid division of the mature cells, hepatocytes, and bile duct epithelial cells. Proliferation of the parenchymal cells is regulated by numerous cytokine/growth factor-mediated pathways and is timely synchronized with extracellular matrix degradation and the restoration of the vasculature. The putative role of stem cells in physiology, pathophysiology, and therapy is not yet precisely known but currently is under intensive investigation. Resident hepatic stem/ progenitor cells have been identified in small numbers and implicated in liver tissue repair, when hepatocyte and bile duct replication capacity is exhausted or experimentally inhibited. Several independent reports have suggested that bone marrow cells can give rise to different hepatic epithelial cells types, including hepatic stem cells, hepatocytes, and bile duct epithelium. These observations have resulted in the hypothesis that extrahepatic stem cells, specifically bone marrow-derived stem cells, are an important source for liver epithelial cell replacement, particularly during chronic injury. Most of published data, however, now suggest that they do not play a relevant role in replacement of epithelial cells in any known form of hepatic injury. In vitro differentiation protocols for various adult extrahepatic stem cells might eventually provide valuable sources of cells for transplantation and therapy. Amniotic epithelial stem cells, fetal liver progenitor cells as well as embryonic stem cells currently emerge as alternative stem cell sources and open new possibilities for cellular therapies of liver disease. 相似文献
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The striatum is divided into two compartments named the patch (or striosome) and the matrix. Although these two compartments can be differentiated by their neurochemical content or afferent and efferent projections, the synaptology of inputs to these striatal regions remains poorly characterized. By using the vesicular glutamate transporters vGluT1 and vGluT2, as markers of corticostriatal and thalamostriatal projections, respectively, we demonstrate a differential pattern of synaptic connections of these two pathways between the patch and the matrix compartments. We also demonstrate that the majority of vGluT2-immunolabeled axon terminals form axospinous synapses, suggesting that thalamic afferents, like corticostriatal inputs, terminate preferentially onto spines in the striatum. Within both compartments, more than 90% of vGluT1-containing terminals formed axospinous synapses, whereas 87% of vGluT2-positive terminals within the patch innervated dendritic spines, but only 55% did so in the matrix. To characterize further the source of thalamic inputs that could account for the increase in axodendritic synapses in the matrix, we undertook an electron microscopic analysis of the synaptology of thalamostriatal afferents to the matrix compartments from specific intralaminar, midline, relay, and associative thalamic nuclei in rats. Approximately 95% of PHA-L-labeled terminals from the central lateral, midline, mediodorsal, lateral dorsal, anteroventral, and ventral anterior/ventral lateral nuclei formed axospinous synapses, a pattern reminiscent of corticostriatal afferents but strikingly different from thalamostriatal projections arising from the parafascicular nucleus (PF), which terminated onto dendritic shafts. These findings provide the first evidence for a differential pattern of synaptic organization of thalamostriatal glutamatergic inputs to the patch and matrix compartments. Furthermore, they demonstrate that the PF is the sole source of significant axodendritic thalamic inputs to striatal projection neurons. These observations pave the way for understanding differential regulatory mechanisms of striatal outflow from the patch and matrix compartments by thalamostriatal afferents. 相似文献
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Jennifer M. De Guzman Ginger Ku Ryan Fahey Yun-Hee Youm Ignatius Kass Donald K. Ingram Vishwa Deep Dixit Indu Kheterpal 《Age (Dordrecht, Netherlands)》2013,35(4):1091-1104
Calorie restriction (CR) remains the most robust metabolic intervention to extend lifespan and improve healthspan in several species. Using global and targeted mass spectrometry-based metabolomics approaches, here we show that chronic CR prevents age-related changes in specific metabolic signatures. Global metabolomic analysis using ultra-performance liquid chromatography–tandem mass spectrometry detected more than 7,000 metabolites in sera from ad-libitum-fed young, aged, and aged C57BL/6 mice maintained on 40 % CR. Multivariate statistical analysis of mass spectrometry data revealed a clear separation among the young, aged, and aged–CR mice demonstrating the potential of this approach for producing reliable metabolic profiles that discriminate based on age and diet. We have identified 168 discriminating features with high statistical significance (p ≤ 0.001) and validated and quantified three of these metabolites using targeted metabolite analysis. Calorie restriction prevented the age-related alteration in specific metabolites, namely lysophosphatidylcholines (16:1 and 18:4), sphingomyelin (d18:1/12:0), tetracosahexaenoic acid, and 7α-dihydroxy-4-cholesten-3-one, in the serum. Pathway analysis revealed that CR impacted the age-related changes in metabolic byproducts of lipid metabolism, fatty acid metabolism, and bile acid biosynthesis. Our data suggest that metabolomics approach has the potential to elucidate the metabolic mechanism of CR’s potential anti-aging effects in larger-scale investigations.
Electronic supplementary material
The online version of this article (doi:10.1007/s11357-012-9430-x) contains supplementary material, which is available to authorized users. 相似文献80.
Akash Deep Chulananda D. A. Goonasekera Yanzhong Wang Joe Brierley 《Intensive care medicine》2013,39(9):1602-1609