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91.
92.
Thomas Thomaidis Corinna Schorn Wolfram Flaig Gerwinn Lingg Elke Schönhals Reinhard Klingel Peter R. Galle Andreas Schwarting 《Journal of clinical apheresis》2009,24(1):37-41
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting multiple organs and tissues. Although there is a wide range of therapeutic applications, the coexistence of severe side effects and contraindications outlines the necessity of new therapeutic options in the treatment of severe RA. We report on the case of a 71‐year‐old patient with successful treatment of a complicated RA with tryptophan immunoadsorption combined with low‐dose steroids. Bacterial spondylitis developed in this patient during long‐term treatment with infliximab and methotrexate. Weekly immunoadsorption sessions with tryptophan columns resulted in continuous suppression of RA activity over a period of more than 5 months, as indicated by laboratory findings, the disease activity score, and the visual analog scale. This is the first report of successful treatment of a refractory and complicated RA using tryptophan immunoadsorption columns. In conclusion, immunoadsorption is a safe and effective therapeutic alternative, which should be considered to bridge infectious complications in patients with severe RA. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
93.
Modulation of matrix metalloproteinase and TIMP-1 expression by cytokines in human RPE cells 总被引:10,自引:0,他引:10
Eichler W Friedrichs U Thies A Tratz C Wiedemann P 《Investigative ophthalmology & visual science》2002,43(8):2767-2773
PURPOSE: The balance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) is crucial for homeostasis of ocular extracellular matrices. To assess altered MMP activity as a determinant in the migration of human retinal pigment epithelial (RPE) cells, expression characteristics of several MMPs and TIMP-1 in RPE cell cultures were investigated. METHODS: Expression studies were performed with RT-PCR, ELISA, and immunofluorescence analysis. Secretion of MMP-2 was demonstrated by zymography. Migration of cytokine-stimulated RPE cells was evaluated with microporous membranes of permeable chambers. RESULTS: MMP-1, -2, -3, and -9; MT2-MMP; and TIMP-1 were expressed in cultured RPE cells. MMP-2 was detected on the cell surface and in secreted inactive and active forms. TGF-beta(2), IL-1beta, and TNF-alpha enhanced secretion of MMP-1, -2, and -3. TGF-beta(2) also stimulated MT2-MMP cell surface expression and release of TIMP-1. The mRNA levels of MMP-1, -2, and -3 and TIMP-1 were markedly increased by TNF-alpha and TGF-beta(2). MMP-2 mRNA levels were also upregulated by PDGF-BB. Migration of RPE cells stimulated by TGF-beta(2) or PDGF-BB was inhibited in presence of a synthetic MMP inhibitor. CONCLUSIONS: Proinflammatory cytokines and TGF-beta(2) play an important role in the upregulation of expression of MMP-1, -2, and -3 in RPE cells and account for a directional shift in the balance between MMPs and TIMPs. Facilitation of RPE cell migration stimulated by cytokines (i.e., TGF-beta(2) or PDGF-BB) in ocular diseases may be due to increased release of MMPs, in the presence of comparatively lower levels of their inhibitors. 相似文献
94.
95.
Eslamboli A Cummings RM Ridley RM Baker HF Muzyczka N Burger C Mandel RJ Kirik D Annett LE 《Experimental neurology》2003,184(1):536-548
Glial cell line-derived neurotrophic factor (GDNF) has shown potential as a treatment for Parkinson's disease. Recombinant adeno-associated viral vectors expressing the GDNF protein (rAAV-GDNF) have been used in rodent models of Parkinson's disease to promote functional regeneration after 6-OHDA lesions of the nigrostriatal system. The goal of the present study was to assess the anatomical and functional efficacy of rAAV-GDNF in the common marmoset monkey (Callithrix jacchus). rAAV-GDNF was injected into the striatum and substantia nigra 4 weeks prior to a unilateral 6-OHDA lesion of the nigrostriatal bundle. Forty percent of the dopamine cells in the lesioned substantia nigra of the rAAV-GDNF-treated monkeys survived, compared with 21% in the untreated monkeys. Fine dopaminergic fibres were observed microscopically in the injected striatum of some rAAV-GDNF-treated monkeys, suggesting that rAAV-GDNF treatment may have prevented, at least in part, the loss of dopaminergic innervation of the striatum. Protection of dopamine cells and striatal fibre innervation was associated with amelioration of the lesion-induced behavioural deficits. rAAV-GDNF-treated monkeys showed partial or complete protection not only in the amphetamine and apomorphine rotation but also in head position and the parkinsonian disability rating scale. Therefore, our study provides evidence for the behavioural and anatomical efficacy of GDNF delivered via an rAAV vector as a possible treatment for Parkinson's disease. 相似文献
96.
97.
Coyne MJ Weinacht KG Krinos CM Comstock LE 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(18):10446-10451
The mammalian gut represents a complex and diverse ecosystem, consisting of unique interactions between the host and microbial residents. Bacterial surfaces serve as an interface that promotes and responds to this dynamic exchange, a process essential to the biology of both symbionts. The human intestinal microorganism, Bacteroides fragilis, is able to extensively modulate its surface. Analysis of the B. fragilis genomic sequence, together with genetic conservation analyses, cross-species cloning experiments, and mutational studies, revealed that this organism utilizes an endogenous DNA inversion factor to globally modulate the expression of its surface structures. This DNA invertase is necessary for the inversion of at least 13 regions located throughout the genome, including the promoter regions for seven of the capsular polysaccharide biosynthesis loci, an accessory polysaccharide biosynthesis locus, and five other regions containing consensus promoter sequences. Bacterial DNA invertases of the serine site-specific recombinase family are typically encoded by imported elements such as phage and plasmids, and act locally on a single region of the imported element. In contrast, the conservation and unique global regulatory nature of the process in B. fragilis suggest an evolutionarily ancient mechanism for surface adaptation to the changing intestinal milieu during commensalism. 相似文献
98.
Kivisäkk P Mahad DJ Callahan MK Trebst C Tucky B Wei T Wu L Baekkevold ES Lassmann H Staugaitis SM Campbell JJ Ransohoff RM 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(14):8389-8394
Cerebrospinal fluid (CSF) from healthy individuals contains between 1,000 and 3,000 leukocytes per ml. Little is known about trafficking patterns of leukocytes between the systemic circulation and the noninflamed CNS. In the current study, we characterized the surface phenotype of CSF cells and defined the expression of selected adhesion molecules on vasculature in the choroid plexus, the subarachnoid space surrounding the cerebral cortex, and the cerebral parenchyma. Using multicolor flow cytometry, we found that CSF cells predominantly consisted of CD4+/CD45RA-/CD27+/CD69+-activated central memory T cells expressing high levels of CCR7 and L-selectin. CD3+ T cells were present in the choroid plexus stroma in autopsy CNS tissue sections from individuals who died without known neurological disorders. P- and E-selectin immunoreactivity was detected in large venules in the choroid plexus and subarachnoid space, but not in parenchymal microvessels. CD4+ T cells in the CSF expressed high levels of P-selectin glycoprotein ligand 1, and a subpopulation of circulating CD4+ T cells displayed P-selectin binding activity. Intercellular adhesion molecule 1, but not vascular cell adhesion molecule 1 or mucosal addressin cell adhesion molecule 1, was expressed in choroid plexus and subarachnoid space vessels. Based on these findings, we propose that T cells are recruited to the CSF through interactions between P-selectin/P-selectin ligands and intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 in choroid plexus and subarachnoid space venules. These results support the overall hypothesis that activated memory T cells enter CSF directly from the systemic circulation and monitor the subarachnoid space, retaining the capacity to either initiate local immune reactions or return to secondary lymphoid organs. 相似文献
99.
Potapov EV Zurbrügg HR Herzke C Srock S Riess H Sodian R Hübler S Hetzer R 《The Annals of thoracic surgery》2002,74(2):384-389
BACKGROUND: Chronic lymphatic leukemia (CLL) is a common disease among elderly individuals. The number of older patients undergoing operations with cardiopulmonary bypass (CPB) is increasing. The aim of the present study was to evaluate the impact of cardiac surgery using CPB on the long-term course of CLL. METHODS: From 1992 to 2000, a total of 28 patients with CLL underwent heart surgery using CPB at our institution (group I). These patients were compared with 25 patients from the CLL register who were retrospectively matched with regard to preoperative administration of chemotherapy, Binet classification, age, and sex (group II). A time-point was selected for each patient in group II so that the variables for the two groups corresponded in relation to the time of operation of the patients in group I. Midterm follow-up data in both groups were analyzed. RESULTS: There were no differences between groups regarding matched variables. The mean follow-up time was similar in both groups (2.6 +/- 2.2 vs 2.3 +/- 1.3 years, p > 0.5). The 30-day mortality in group I was 14.3%. The mean stay in the intensive care unit was 4.2 +/- 7.5 days; the median number of units of packed red blood cells transfused was three (range 0 to 17). Compared with group II, in group I significantly fewer patients (11 vs 17, p = 0.049) required chemotherapy significantly later (1.98 +/- 2.06 vs 0.84 +/- 1.18 years, p = 0.018). During follow-up, no difference was found between groups regarding severe infections (10 vs 14, p = 0.14). Despite postoperative mortality in group I, the long-term mortality was similar in both groups (p = 0.3). CONCLUSIONS: Cardiac surgery using CPB did not have a negative impact on the natural course of CLL. Moreover, this procedure seems to be associated with a decrease in the number of postoperative chemotherapy administrations and with an increase of chemotherapy-free survival time. Although CLL may be a risk factor in the early postoperative period, it is not a contraindication for cardiac surgery using CPB. 相似文献
100.
The aim of this study was to investigate the effect of high dietary iron concentrations on the antioxidant status of rats fed two different types of fat. Four groups of male adult Sprague-Dawley rats were fed diets with adequate (50 mg iron supplemented per kg diet) or high (500 mg iron supplemented per kg diet) iron concentrations with either lard or salmon oil as dietary fat at 100 g/kg for 12 wk. The antioxidant status of the rats was profoundly influenced by the type of fat. Rats fed salmon oil diets had higher concentrations of thiobarbituric acid-reactive substances (TBARS) (P < 0.001), various cholesterol oxidation products (COP) (P < 0.001), total and oxidized glutathione (P < 0.05) and a lower concentration of alpha-tocopherol (P < 0.05) in liver and plasma than rats fed lard diets. The iron concentration of the diet did not influence the concentrations of TBARS, the activities of superoxide dismutase and glutathione peroxidase or the concentration of alpha-tocopherol in plasma or liver. The activity of catalase (P < 0.01) and the concentrations of total, oxidized and reduced glutathione (P < 0.05) in liver were slightly but significantly higher in rats fed high iron diets than in rats fed adequate iron diets, irrespective of the dietary fat. Rats fed the high iron diets with salmon oil, moreover, had higher concentrations of various COP in the liver (P < 0.001) than rats fed adequate iron diets with salmon oil. These results suggest that feeding a high iron diet does not generally affect the antioxidant status of rats but enhances the formation of COP, particularly if the diet is rich in polyunsaturated fatty acids. 相似文献