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Anthony J. Bonito Costica Aloman M. Isabel Fiel Nichole M. Danzl Sungwon Cha Erica G. Weinstein Seihwan Jeong Yongwon Choi Matthew C. Walsh Konstantina Alexandropoulos 《The Journal of clinical investigation》2013,123(8):3510-3524
TRAF6, an E3 ubiquitin protein ligase, plays a critical role in T cell tolerance by regulating medullary thymic epithelial cell (mTEC) development. mTECs regulate T cell tolerance by ectopically expressing self-antigens and eliminating autoreactive T cells in the thymus. Here we show that mice with mTEC depletion due to conditional deletion of Traf6 expression in murine thymic epithelial cells (Traf6ΔTEC mice) showed a surprisingly narrow spectrum of autoimmunity affecting the liver. The liver inflammation in Traf6ΔTEC mice exhibited all the histological and immunological characteristics of human autoimmune hepatitis (AIH). The role of T cells in AIH establishment was supported by intrahepatic T cell population changes and AIH development after transfer of liver T cells into immunodeficient mice. Despite a 50% reduction in natural Treg thymic output, peripheral tolerance in Traf6ΔTEC mice was normal, whereas compensatory T regulatory mechanisms were evident in the liver of these animals. These data indicate that mTECs exert a cell-autonomous role in central T cell tolerance and organ-specific autoimmunity, but play a redundant role in peripheral tolerance. These findings also demonstrate that Traf6ΔTEC mice are a relevant model with which to study the pathophysiology of AIH, as well as autoantigen-specific T cell responses and regulatory mechanisms underlying this disease. 相似文献
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Konstantina Patouni Ondrej Cinek Stepanka Pruhova Lenka Elblova Maria Xatzipsalti Amalia Sertedaki Andriani Vazeou 《European journal of medical genetics》2021,64(9):104264
BackgroundMaturity onset diabetes of the young (MODY) is the most commonly reported form of monogenic diabetes in the pediatric population. Only a few cases of digenic MODY have been reported up to now.Case reportA female patient was diagnosed with diabetes at the age of 7 years and was treated with insulin. A strong family history of diabetes was present in the maternal side of the family. The patient also presented hypomagnesemia, glomerulocystic kidney disease and a bicornuate uterus. Genetic testing of the patient revealed that she was a double heterozygous carrier of HNF1A gene variant c.685C > T; (p.Arg229Ter) and a whole gene deletion of the HNF1B gene. Her mother was a carrier of the same HNF1A variant.ConclusionDigenic inheritance of MODY pathogenic variants is probably more common than currently reported in literature. The use of Next Generation Sequencing panels in testing strategies for MODY could unmask such cases that would otherwise remain undiagnosed. 相似文献
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A ten‐year review of soft tissue reactions around percutaneous titanium implants for auricular prosthesis 下载免费PDF全文
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Dervenoulas J Tsirigotis P Bollas G Koumarianou AA Pappa V Mantzios G Xiros N Economopoulos T Papageorgiou E Pappa M Raptis SA 《Acta haematologica》2001,105(4):204-208
Thrombotic thrombocytopaenic purpura (TTP) is characterised by platelet aggregation in the capillaries, thrombocytopaenia and microangiopathic haemolytic anaemia that result in organ ischaemia, mainly of the CNS and kidneys. Since the institution of plasma exchange therapy no further treatments have been proved to improve the survival and the relapse rate of TTP patients. In this retrospective study, we evaluated the efficacy of normal human immunoglobulin treatment in 44 patients suffering from TTP. Patients were divided into two groups that either did not receive (group A: 15 patients) or received (group B: 29 patients) 400 mg/kg of human normal immunoglobulin intravenously (ivIgG) for 5 days. All patients received treatment with corticosteroids, anti-platelet agents and plasma exchange. The results clearly showed that there was no statistically significant difference between the two groups in either remission rate or time to relapse following remission. In conclusion, this study did not prove any beneficial effect of ivIgG in the treatment of TTP patients. 相似文献
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Maria Drakopoulou George Oikonomou Stergios Soulaidopoulos Basil Thanopoulos Konstantina Aggeli Dimitrios Tousoulis Konstantinos Toutouzas 《Congenital heart disease》2020,15(3):147-151
The percutaneous closure of ostium secundum atrial septal defects
(ASD) is a well-established procedure. Currently available devices and delivery
systems are designed to be used via the femoral venous route. However, an
alternative approach needs to be considered in cases of congenital or acquired
caval obstruction. We describe a successful transjugular closure of a moderate
sized secundum ASD with the Cocoon Septal Occluder in a 37-year-old
symptomatic woman with inferior vena cava (IVC) thrombosis, using a novel
deployment technique to overcome difficulties, namely maintaining stable sheath
position in the left atrium. Percutaneous closure of secundum ASDs via the
transjugular approach is safe, feasible and effective and can be a reasonable
alternative to surgical closure in patients with failed femoral venous access and
not anatomically complex atrial septal defects. 相似文献
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Estrogens' effects on hearing are documented across species, but the responsible molecular mechanisms remain unknown. The presence of estrogen receptors (ER) throughout the auditory system offers a potential pathway of direct estrogenic effects on auditory function, but little is known about how each ER's expression is regulated by the overall hormonal status of the body. In the present study, we determined the effects of ovariectomy and chronic 17β-estradiol treatment on mRNA and protein expression of ERα and ERβ in peripheral (cochlea) and central (inferior colliculus) auditory structures of mice, as well as on auditory-related behavior using the acoustic startle response (ASR), prepulse inhibition (PPI), and habituation of the startle response. 17β-Estradiol treatment down-regulated ERα but not ERβ and increased PPI and latency of the ASR. Neither the magnitude nor the habituation of ASR was affected. Furthermore, ER's mRNA and protein expression in the inner ear were analyzed throughout the estrous cycle (proestrus, estrus, metestrus, and diestrus), revealing a negative correlation of circulating estrogens with ERα expression, whereas ERβ was stable. Our findings show that ER not only are present in both the peripheral and central auditory system but also that circulating estrogen levels down-regulate ERα expression in the auditory system and affect PPI and the latency of ASR, suggesting a key role of ERα as a hormone-induced modulator of the auditory system and behavior. 相似文献
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