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《Expert review of anti-infective therapy》2013,11(3):359-362
miRNAs are short, nonprotein coding RNAs that regulate target gene expression principally by causing translational repression and/or mRNA degradation. miRNAs are involved in most mammalian biological processes and have pivotal roles in controlling the expression of factors involved in basal and stimulus-induced signaling pathways. Considering their central role in the regulation of gene expression, miRNAs represent therapeutic drug targets. Here we describe how miRNAs are involved in the regulation of aspects of innate immunity and inflammation, what happens when this goes awry, such as in the chronic inflammatory lung diseases cystic fibrosis and asthma, and discuss the current state-of-the-art miRNA-targeted therapeutics. 相似文献
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Nina Reistad Jan H. Nilsson Magnus Bergenfeldt Pehr Rissler Christian Sturesson 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2019,21(2):175-180
Background
Liver steatosis is associated with poor outcome after liver transplantation and liver resection. There is a need for an accurate and reliable intraoperative tool to identify and quantify steatosis. This study aimed to investigate whether surface diffuse reflectance spectroscopy (DRS) measurements could detect liver steatosis on humans during liver surgery.Methods
The DRS instrumentation setup consists of a computer, a high-power tungsten halogen light source and two spectrometers, connected through a trifurcated optical fiber to a hand-held probe. Patients scheduled for open resection for liver tumors were considered for inclusion. Multiple DRS measurements were performed on the liver surface after mobilization.Results
In total, 1210 DRS spectra originated from 38 patients, were analyzed. When applying the data to an analytical model the volumetric absorption ratio factor of fat and water specified an explicit distinction between mild to moderate, and moderate to severe steatosis (p < 0.001). There were significant differences between none-to-mild and moderate-to-severe steatosis grade for the following parameters: reduced scattering coefficient (p < 0.001), Mie to total scattering fraction (p < 0.001), Mie slope (p = 0.003), lipid/(lipid + water) (p < 0.001), blood volume (p = 0.044) and bile volume (p < 0.001).Conclusion
This study shows that it is possible to evaluate steatosis grades with hepatic surface diffuse reflectance spectroscopy measurements. 相似文献17.
J. Devon Roll Ashley G. Rivenbark Rupninder Sandhu Joel S. Parker Wendell D. Jones Lisa A. Carey Chad A. Livasy William B. Coleman 《Experimental and molecular pathology》2013
A subset of human breast cancer cell lines exhibits aberrant DNA hypermethylation that is characterized by hyperactivity of the DNA methyltransferase enzymes, overexpression of DNMT3b, and concurrent methylation-dependent silencing of numerous epigenetic biomarker genes. The objective of this study was to determine if this aberrant DNA hypermethylation (i) is found in primary breast cancers, (ii) is associated with specific breast cancer molecular subtypes, and (iii) influences patient outcomes. Analysis of epigenetic biomarker genes (CDH1, CEACAM6, CST6, ESR1, GNA11, MUC1, MYB, SCNN1A, and TFF3) identified a gene expression signature characterized by reduced expression levels or loss of expression among a cohort of primary breast cancers. The breast cancers that express this gene expression signature are enriched for triple-negative subtypes — basal-like and claudin-low breast cancers. Methylation analysis of primary breast cancers showed extensive promoter hypermethylation of epigenetic biomarker genes among triple-negative breast cancers, compared to other breast cancer subclasses where promoter hypermethylation events were less frequent. Furthermore, triple-negative breast cancers either did not express or expressed significantly reduced levels of protein corresponding to methylation-sensitive biomarker gene products. Together, these findings suggest strongly that loss of epigenetic biomarker gene expression is frequently associated with gene promoter hypermethylation events. We propose that aberrant DNA hypermethylation is a common characteristic of triple-negative breast cancers and may represent a fundamental biological property of basal-like and claudin-low breast cancers. Kaplan–Meier analysis of relapse-free survival revealed a survival disadvantage for patients with breast cancers that exhibit aberrant DNA hypermethylation. Identification of this distinguishing trait among triple-negative breast cancers forms the basis for development of new rational therapies that target the epigenome in patients with basal-like and claudin-low breast cancers. 相似文献
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Nabila Seddiki Chansavath Phetsouphanh Sanjay Swaminathan Yin Xu Sudha Rao Jasmine Li Elissa L. Sutcliffe Gareth Denyer Robert Finlayson Linda Gelgor David A. Cooper John Zaunders Anthony D. Kelleher 《European journal of immunology》2013,43(2):510-520
The fine control of T‐cell differentiation and its impact on HIV disease states is poorly understood. In this study, we demonstrate that B‐lymphocyte‐induced maturation protein‐1 (Blimp‐1/Prdm1) is highly expressed in CD4+ T cells from chronically HIV‐infected (CHI) patients compared to cells from long‐term nonprogressors or healthy controls. Stimulation through the T‐cell receptor in the presence ofIL‐2 induces Blimp‐1 protein expression. We show here that Blimp‐1 levels are translationally regulated by microRNA‐9 (miR‐9). Overexpression of miR‐9 induces Blimp‐1 repression, restoring IL‐2 secretion in CD4+ T cells via reduction in the binding of Blimp‐1 to the il‐2 promoter. In CHI patients where IL‐2 expression is reduced and there is generalized T‐cell dysfunction, we show differential expression of both miR‐9 and Blimp‐1 in CD4+ cells compared with levels in long‐term nonprogressors. These data identify a novel miR‐9/Blimp‐1/IL‐2 axis that is dysregulated in progressive HIV infection. 相似文献
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Catharina Müller Oskar Rosmark Emma Åhrman Hans Brunnström Katharina Wassilew Annika Nybom Barbora Michaliková Hillevi Larsson Leif T. Eriksson Hans H. Schultz Michael Perch Johan Malmström Jenny Wigén Martin Iversen Gunilla Westergren-Thorsson 《The American journal of pathology》2021,191(8):1398-1411