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排序方式: 共有502条查询结果,搜索用时 593 毫秒
191.
Findings from the Human Genome Project (HGP) suggest that tremendous opportunities exist for increased life expectancies and improved quality of life. The findings also raise enormous concerns about ethical, legal, and psychosocial implications, particularly for underrepresented and vulnerable populations. This article proposes an education model that focuses on genetically informed, ethical practice that will help social worker practitioners and educators play a more effective role as they confront the many implications of genetic and genomic research in the 21st century. 相似文献
192.
Schmidt LS Thomsen M Weikop P Dencker D Wess J Woldbye DP Wortwein G Fink-Jensen A 《Psychopharmacology》2011,216(3):367-378
Rationale
The reinforcing effects of cocaine are mediated by the mesolimbic dopamine system. Behavioral and neurochemical studies have shown that the cholinergic muscarinic M4 receptor subtype plays an important role in regulation of dopaminergic neurotransmission. 相似文献193.
Koener B Goursaud S Van De Stadt M Calas AG Jeanjean AP Maloteaux JM Hermans E 《Naunyn-Schmiedeberg's archives of pharmacology》2011,383(1):65-77
The partial agonist profile of novel antipsychotics such as aripiprazole has hardly been demonstrated in biochemical assays on animal tissues. As it is established that responses induced by dopamine D? receptor agonists are increased in models of dopaminergic sensitization, this paradigm was used in order to facilitate the detection of the partial agonist properties of aripiprazole. At variance with all other partial and full agonists tested, the partial agonist properties of aripiprazole were not revealed in guanosine 5′-O-(γ-[3?S]thiotriphosphate ([3?S]GTPγS) binding assays on striatal membranes from haloperidol-treated rats. Hence,aripiprazole behaved as an antagonist, efficiently inhibiting the functional response to dopamine. Similarly, in behavioural assays, aripiprazole dose-dependently inhibited the stereotypies elicited by apomorphine. However, at variance with haloperidol, repeated administrations of aripiprazole(3 weeks) at the doses of 10 and 30 mg/kg did not induce any up-regulation or hyperfunctionality of the dopamine D? receptors in the striatum. These data highlight the putative involvement of other pharmacological targets for aripiprazole that would support in the prevention of secondary effects commonly associated with the blockade of striatal dopamine D? receptors. Hence, in additional experiments, aripiprazole was found to efficiently promote [3?S]GTPγS binding in hippocampal membranes through the activation of 5-HT(?A) receptors. Further experiments investigating the second messenger cascades should be performed so as to establish the functional properties of aripiprazole and understand the mechanism underlying the prevention of dopamine receptor regulation in spite of the observed antagonism. 相似文献
194.
Pierre-Edouard Debureaux Pierre Bourrier Pierre Emmanuel Rautou Anne-Marie Zagdanski Morgane De Boutiny Simona Pagliuca Aurlien Sutra de Galy Marie Robin Rgis Peffault de Latour Aurlie Plessier Flore Sicre de Fontbrune Alinor Xhaard Pedro Henrique Prata Dominique Valla Grard Socie David Michonneau 《Haematologica》2021,106(9):2374
Significant morbidity and mortality have been associated with liver complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Causes and consequences of these hepato-biliary complications are various and might be life-threatening. A high misdiagnosis rate has been reported because of a weak correlation between clinical, laboratory and imaging data. Liver elastography, a liver stiffness measure, is able to assess liver fibrosis and portal hypertension in most liver diseases, but data after allo-HSCT are scarce. Our aim was to determine the interest of sequential liver stiffness measurements for the diagnosis of early hepatic complications after allo-HSCT. Over a 2-year time period, 161 consecutive adult patients were included and 146 were analyzed. Ultrasonography and elastography measurements were performed before transplantation, at day+7 and day+14 by three different experienced radiologists unaware of the patients’ clinical status. Eightyone (55%) patients had liver involvements within the first 100 days after allo-HSCT. Baseline elastography was not predictive for the occurrence of overall liver abnormalities. A significant increase in two-dimensional real-time shearwave elastography (2D-SWE) was found in patients with sinusoidal obstruction syndrome (SOS). Fifteen patients (10%) fulfilled European Society for Blood and Marrow Transplantation (EBMT) score criteria and twelve (8%) reached Baltimore criteria for SOS diagnosis, but only six (4%) had a confirmed SOS. 2D-SWE at day+14 allowed early detection of SOS (AUROC=0.84, P=0.004) and improved sensibility (75%), specificity (99%) and positive predictive value (60%) over the Seattle, Baltimore or EBMT scores. A 2D-SWE measurement above 8.1 kPa at day+14 after allo-HSCT seems a promising, non-invasive, and reproducible tool for early and accurate diagnosis of SOS. 相似文献
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198.
Meyre D Farge M Lecoeur C Proenca C Durand E Allegaert F Tichet J Marre M Balkau B Weill J Delplanque J Froguel P 《Human molecular genetics》2008,17(12):1798-1802
Stone et al. previously reported an association between the TBC1D1 gene variant R125W (rs35859249) and severe obesity in women from US pedigrees. We attempted to replicate this result in 9714 French Caucasian individuals, combining family-based and general population studies. We confirmed an association with familial obesity (defined as body mass index (BMI) > or = 97th percentile) in women from 1109 obesity-selected pedigrees (Z-score = 2.70, P = 0.008). Analysis of 16 microsatellite markers on chromosome 4 restricted to the 42 pedigrees carrying the TBC1D1 R125W variant allele also revealed a suggestive evidence of linkage with obesity (maximum likelihood binomial LOD of 2.73, P = 0.0002) on chromosome 4p14, where resides TBC1D1. In contrast, R125W variant was neither associated with BMI nor with obesity in a large population-based cohort. These results confirm a putative role of TBC1D1 R125W variant in familial obesity predisposition. 相似文献
199.
Stum M Girard E Bangratz M Bernard V Herbin M Vignaud A Ferry A Davoine CS Echaniz-Laguna A René F Marcel C Molgó J Fontaine B Krejci E Nicole S 《Human molecular genetics》2008,17(20):3166-3179
Schwartz-Jampel syndrome (SJS) is a recessive neuromyotonia with chondrodysplasia. It results from hypomorphic mutations of the gene encoding perlecan, leading to a decrease in the levels of this heparan sulphate proteoglycan in basement membranes (BMs). It has been suggested that SJS neuromyotonia may result from endplate acetylcholinesterase (AChE) deficiency, but this hypothesis has never been investigated in vivo due to the lack of an animal model for neuromyotonia. We used homologous recombination to generate a knock-in mouse strain with one missense substitution, corresponding to a human familial SJS mutation (p.C1532Y), in the perlecan gene. We derived two lines, one with the p.C1532Y substitution alone and one with p.C1532Y and the selectable marker Neo, to down-regulate perlecan gene activity and to test for a dosage effect of perlecan in mammals. These two lines mimicked SJS neuromyotonia with spontaneous activity on electromyogramm (EMG). An inverse correlation between disease severity and perlecan secretion in the BMs was observed at the macroscopic and microscopic levels, consistent with a dosage effect. Endplate AChE levels were low in both lines, due to synaptic perlecan deficiency rather than major myofibre or neuromuscular junction disorganization. Studies of muscle contractile properties showed muscle fatigability at low frequencies of nerve stimulation and suggested that partial endplate AChE deficiency might contribute to SJS muscle stiffness by potentiating muscle force. However, physiological endplate AChE deficiency was not associated with spontaneous activity at rest on EMG in the diaphragm, suggesting that additional changes are required to generate such activity characteristic of SJS. 相似文献