全文获取类型
收费全文 | 3024篇 |
免费 | 233篇 |
国内免费 | 11篇 |
专业分类
耳鼻咽喉 | 30篇 |
儿科学 | 97篇 |
妇产科学 | 77篇 |
基础医学 | 501篇 |
口腔科学 | 66篇 |
临床医学 | 252篇 |
内科学 | 638篇 |
皮肤病学 | 129篇 |
神经病学 | 403篇 |
特种医学 | 59篇 |
外科学 | 229篇 |
综合类 | 15篇 |
一般理论 | 1篇 |
预防医学 | 259篇 |
眼科学 | 37篇 |
药学 | 227篇 |
中国医学 | 4篇 |
肿瘤学 | 244篇 |
出版年
2024年 | 6篇 |
2023年 | 60篇 |
2022年 | 89篇 |
2021年 | 186篇 |
2020年 | 98篇 |
2019年 | 143篇 |
2018年 | 125篇 |
2017年 | 93篇 |
2016年 | 104篇 |
2015年 | 134篇 |
2014年 | 161篇 |
2013年 | 156篇 |
2012年 | 273篇 |
2011年 | 267篇 |
2010年 | 133篇 |
2009年 | 114篇 |
2008年 | 176篇 |
2007年 | 152篇 |
2006年 | 141篇 |
2005年 | 158篇 |
2004年 | 100篇 |
2003年 | 126篇 |
2002年 | 95篇 |
2001年 | 25篇 |
2000年 | 17篇 |
1999年 | 16篇 |
1998年 | 10篇 |
1997年 | 13篇 |
1996年 | 10篇 |
1995年 | 11篇 |
1994年 | 9篇 |
1993年 | 7篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 11篇 |
1989年 | 6篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1982年 | 2篇 |
1980年 | 3篇 |
1978年 | 3篇 |
1971年 | 1篇 |
1964年 | 1篇 |
1932年 | 1篇 |
1931年 | 2篇 |
1930年 | 2篇 |
1929年 | 5篇 |
1903年 | 1篇 |
排序方式: 共有3268条查询结果,搜索用时 406 毫秒
61.
62.
63.
64.
65.
Bianca E. Schneider Jochen Behrends Kristine Hagens Nadine Harmel James A. Shayman Ulrich E. Schaible 《European journal of immunology》2014,44(8):2394-2404
Phospholipases catalyze the cleavage of membrane phospholipids into smaller bioactive molecules. The lysosomal phospholipase A2 (LPLA2) is specifically expressed in macrophages. LPLA2 gene deletion in mice causes lysosomal phospholipid accumulation in tissue macrophages leading to phospholipidosis. This phenotype becomes most prominent in alveolar macrophages where LPLA2 contributes to surfactant phospholipid degradation. High expression of LPLA2 in alveolar macrophages prompted us to investigate its role in host immunity against the respiratory pathogen Mycobacterium tuberculosis, the causative agent of tuberculosis. Here we report that adaptive immune responses to M. tuberculosis were impaired in LPLA2 deficient mice. Upon aerosol infection with M. tuberculosis, LPLA2 deficient mice showed enhanced mycobacterial counts but less lung immunopathology and pulmonary inflammatory responses. Compromised T‐cell priming in the lymph nodes was associated with impaired pulmonary T‐cell recruitment and activation. Together with reduced Th1 type cytokine production, these results indicate that LPLA2 is indispensable for the induction of adaptive T‐cell immunity to M. tuberculosis. Taken together, we identified an unexpected and novel function of a lysosomal phospholipid‐degrading enzyme. 相似文献
66.
Silvana G.P. Campos Bianca F. Gonçalves Wellerson R. Scarano Rejane M. Góes Sebastião R. Taboga 《Acta histochemica》2014
The gerbil is a rodent considered a good model for studies of prostatic morphophysiology under different experimental conditions. Studies involving castration and steroidal blockers of aged gerbils showed that the glandular epithelium persists after long-term therapy, preventing the organ atrophy. Thus, the objective of this study was to evaluate the phenotypic characteristics and behavior of prostatic epithelial cells that remained after different periods of hormone ablation in aged gerbils. The identification of elements that influenced the survival of this cell type was performed by morphometric, nuclear phenotypes, ultrastructural and immune histochemical analysis. The most significant responses to treatment, by analyzing morphometric features, were observed during the first three time points (day 1, day 3, and day 7), after which there appeared to be an adjustment of the gland to the hormone ablation. All treatments led to changes in the state of chromatin condensation, DNA methylation pattern and phenotypic changes indicated cell senescence. Additionally, an increase in the basal cells seemed to guarantee self-renewal properties to the epithelium. These data indicate that changes occur at many levels, including gene expression and nuclear architecture in the epithelial cells, when aging and steroidal blockade are associated. These aspects are important when considering castration-resistant prostate cancer, a malignant tumor posing difficult therapeutic intervention. 相似文献
67.
68.
Christoph Bartenhagen Vera Okpanyi Michael Gombert Birte Moehlendick Bianca Behrens Hans‐Ulrich Klein Harald Rieder Pina Fanny Ida Krell Martin Dugas Nikolas Hendrik Stoecklein Arndt Borkhardt 《Human mutation》2014,35(10):1260-1270
Unbiased amplification of the whole‐genome amplification (WGA) of single cells is crucial to study cancer evolution and genetic heterogeneity, but is challenging due to the high complexity of the human genome. Here, we present a new workflow combining an efficient adapter‐linker PCR‐based WGA method with second‐generation sequencing. This approach allows comparison of single cells at base pair resolution. Amplification recovered up to 74% of the human genome. Copy‐number variants and loss of heterozygosity detected in single cell genomes showed concordance of up to 99% to pooled genomic DNA. Allele frequencies of mutations could be determined accurately due to an allele dropout rate of only 2%, clearly demonstrating the low bias of our PCR‐based WGA approach. Sequencing with paired‐end reads allowed genome‐wide analysis of structural variants. By direct comparison to other WGA methods, we further endorse its suitability to analyze genetic heterogeneity. 相似文献
69.
David Gilfillan Gordon Parker Elizabeth Sheppard Vijaya Manicavasagar Amelia Paterson Bianca Blanch Stacey McCraw 《Comprehensive psychiatry》2014
Objective
This paper seeks to determine the relevance and likely salience of cognitive behaviour therapy (CBT) as a treatment for melancholic depression.Methods
The findings of a randomised trial comparing 12-week outcome of 18 patients with melancholic depression receiving antidepressant medication and 11 receiving CBT were evaluated, and qualitative explanations for the outcomes were provided principally by the treating CBT practitioners.Results
In the trial, CBT showed no improvement in depression severity in the first four weeks and then some level of improvement over the subsequent eight weeks. Outcome was superior for those receiving antidepressant medication at 12 weeks and was first demonstrated at four weeks. The benefits of CBT appeared to be in settling anxiety, dealing with cognitive processing of having a melancholic depression and addressing any personality vulnerabilities.Conclusion
While a pilot study, our qualitative reports indicate that CBT may provide a useful role in managing melancholia as an adjunct to antidepressant medication. Future studies examining such a combination treatment model should seek to determine if indicative data provided here argue for a sequencing model of CBT being introduced after medication has addressed core biological underpinnings. 相似文献70.
Timmers S Nabben M Bosma M van Bree B Lenaers E van Beurden D Schaart G Westerterp-Plantenga MS Langhans W Hesselink MK Schrauwen-Hinderling VB Schrauwen P 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(29):11711-11716
A low fat oxidative capacity has been linked to muscle diacylglycerol (DAG) accumulation and insulin resistance. Alternatively, a low fat oxidation rate may stimulate glucose oxidation, thereby enhancing glucose disposal. Here, we investigated whether an ethyl-2-[6-(4-chlorophenoxy)hexyl]-oxirane-2-carboxylate (etomoxir)-induced inhibition of fat oxidation leads to muscle fat storage and insulin resistance. An intervention in healthy male subjects was combined with studies in human primary myotubes. Furthermore, muscle DAG and triacylglycerol (TAG), mitochondrial function, and insulin signaling were examined in etomoxir-treated C57bl6 mice. In humans, etomoxir administration increased glucose oxidation at the expense of fat oxidation. This effect was accompanied by an increased abundance of GLUT4 at the sarcolemma and a lowering of plasma glucose levels, indicative of improved glucose homeostasis. In mice, etomoxir injections resulted in accumulation of muscle TAG and DAG, yet improved insulin-stimulated GLUT4 translocation. Also in human myotubes, insulin signaling was improved by etomoxir, in the presence of increased intramyocellular lipid accumulation. These insulin-sensitizing effects in mice and human myotubes were accompanied by increased phosphorylation of AMP-activated protein kinase (AMPK). Our results show that a reduction in fat oxidation leading to accumulation of muscle DAG does not necessarily lead to insulin resistance, as the reduction in fat oxidation may activate AMPK. 相似文献