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排序方式: 共有816条查询结果,搜索用时 125 毫秒
91.
Ingmar Mederacke Karsten Wursthorn Janina Kirschner Kinan Rifai Michael P. Manns Heiner Wedemeyer Matthias J. Bahr 《Liver international》2009,29(10):1500-1506
Background and aims: Transient elastography is increasingly being used in patients with chronic liver disease. It has proven particularly useful to identify patients with advanced fibrosis or cirrhosis, while classification of no or little fibrosis appears to be difficult. In general, stiffness values <6 kPa are considered normal, whereas patients with higher levels are candidates for a disease‐specific treatment or further diagnostic evaluation. Parameters influencing liver stiffness may include food intake that increases liver blood flow. Methods: In a pilot study, transient elastography was performed in eight patients with chronic hepatitis C at fasting and serially for 180 min after intake of a standardized breakfast. Confirmatory, 56 patients and 19 controls underwent liver stiffness determination at fasting, directly after meal intake and 1 h after breakfast. Results: Liver stiffness significantly increased immediately after food intake for up to 60 min (P=0.01) before normalizing after 180 min. An intraindividual analysis showed a significant increase in 22 out of 43 patients with an initial liver stiffness ≤10 kPa. An increase of at least 1 kPa after food intake was found in 24 out of 43 (56%) patients with initial stiffness ≤10 kPa. Notably, nine out of 23 (39%) patients with normal initial liver stiffness (<6 kPa) had a value of >6 kPa after food intake, potentially leading to unnecessary treatment or diagnostic procedures. Conclusion: Food intake increases liver stiffness in patients with hepatitis C virus infection and healthy controls. To standardize liver stiffness evaluation, we suggest measurement in the fasting condition. 相似文献
92.
Ingmar Meinecke Gza Pap Heidi Mendoza Steffen Drange Stephan Ender Simon Strietholt Renate E. Gay Christine Seyfert Barbara Ink Steffen Gay Thomas Pap Marvin A. Peters 《Arthritis \u0026amp; Rheumatology》2009,60(7):2065-2070
Objective
To study the expression of small ubiquitin‐like modifier 1 (SUMO‐1) in aseptic loosening of prosthesis implants and to investigate its role in regulating the susceptibility of prosthesis‐loosening fibroblast‐like synoviocytes (FLS) to Fas‐induced apoptosis.Methods
Specimens of aseptically loosened tissue were obtained at revision surgery, and the expression of SUMO‐1 was analyzed by in situ hybridization. SUMO‐1 levels in FLS were determined by quantitative polymerase chain reaction and Western blot analysis. Immunohistochemistry and confocal microscopy were used to study the subcellular localization of SUMO‐1. The functional role of SUMO‐1 in Fas‐induced apoptosis of prosthesis‐loosening FLS was investigated by small interfering RNA–mediated knockdown of SUMO‐1 and by gene transfer of the nuclear SUMO‐specific protease SENP1.Results
SUMO‐1 was expressed strongly in aseptically loosened tissue and was found prominently at sites adjacent to bone. Prosthesis‐loosening FLS expressed levels of SUMO‐1 similar to the levels expressed by rheumatoid arthritis (RA) FLS, with SUMO‐1 being found mainly in promyelocytic leukemia protein nuclear bodies. Knockdown of SUMO‐1 had no effect on spontaneous apoptosis but significantly increased the susceptibility of prosthesis‐loosening FLS to Fas‐induced apoptosis. Gene transfer of the nuclear SUMO‐specific protease SENP1 reverted the apoptosis‐inhibiting effects of SUMO‐1.Conclusion
These data suggest that SUMO‐1 is involved in the activation of both RA FLS and prosthesis‐loosening FLS by preventing these cells from undergoing apoptosis. Modification of nuclear proteins by SUMO‐1 contributes to the antiapoptotic effects of SUMO‐1 in prosthesis‐loosening FLS, providing evidence for the specific activation of sumoylation during their differentiation. Therefore, SUMO‐1 may be an interesting target for novel strategies to prevent aseptic prosthesis loosening.93.
Bruns I Steidl U Kronenwett R Fenk R Graef T Rohr UP Neumann F Fischer J Scheid C Hübel K Haas R Kobbe G 《Transfusion》2006,46(2):180-185
BACKGROUND: Current regimens for peripheral blood progenitor cell (PBPC) mobilization in patients with multiple myeloma are based on daily subcutaneous injections of granulocyte-colony-stimulating factor (G-CSF) starting shortly after cytotoxic therapy. Recently a polyethylene glycol-conjugated G-CSF (pegfilgrastim) was introduced that has a substantially longer t(1/2) than the original formula. STUDY DESIGN AND METHODS: The use of pegfilgrastim was examined at two dose levels for PBPC mobilization in patients with Stage II or III multiple myeloma. Four days after cytotoxic therapy with cyclophosphamide (4 g/m(2)), a single dose of either 6 mg pegfilgrastim (n = 15) or 12 mg pegfilgrastim (n = 15) or daily doses of 8 microg per kg unconjugated G-CSF (n = 15) were administered. The number of circulating CD34+ cells was determined during white blood cell (WBC) recovery, and PBPC harvesting was performed by large-volume apheresis. RESULTS: Pegfilgrastim was equally potent at 6 and 12 mg with regard to mobilization and yield of CD34+ cells. No dose dependence was observed because CD34+ cell concentration peaks were 131 and 85 per microL, respectively, and CD34+ cell yield was 10.2 x 10(6) and 7.4 x 10(6) per kg of body weight, respectively. Pegfilgrastim in either dose was associated with a more rapid WBC recovery (p = 0.03) and an earlier performance of the first apheresis procedure (p < 0.05) in comparison to unconjugated G-CSF. No difference regarding CD34+ cell maximum and yield could be observed. CONCLUSION: A single dose of 6 mg pegfilgrastim is equally potent as 12 mg for mobilization and harvest of PBPCs in patients with multiple myeloma. Because no dose dependency was seen at these dose levels, this might be also true for even smaller doses. 相似文献
94.
Eyüpoglu IY Hahnen E Tränkle C Savaskan NE Siebzehnrübl FA Buslei R Lemke D Wick W Fahlbusch R Blümcke I 《Molecular cancer therapeutics》2006,5(5):1248-1255
Inhibitors of histone deacetylases are promising compounds for the treatment of cancer but have not been systematically explored in malignant brain tumors. Here, we characterize the benzamide MS-275, a class I histone deacetylase inhibitor, as potent drug for experimental therapy of glioblastomas. Treatment of four glioma cell lines (U87MG, C6, F98, and SMA-560) with MS-275 significantly reduced cell growth in a concentration-dependent manner (IC(90), 3.75 micromol/L). Its antiproliferative effect was corroborated using a bromodeoxyuridine proliferation assay and was mediated by G(0)-G(1) cell cycle arrest (i.e., up-regulation of p21/WAF) and apoptotic cell death. Implantation of enhanced green fluorescent protein-transfected F98 glioma cells into slice cultures of rat brain confirmed the cytostatic effect of MS-275 without neurotoxic damage to the organotypic neuronal environment in a dose escalation up to 20 micromol/L. A single intratumoral injection of MS-275 7 days after orthotopic implantation of glioma cells in syngeneic rats confirmed the chemotherapeutic efficacy of MS-275 in vivo. Furthermore, its propensity to pass the blood-brain barrier and to increase the protein level of acetylated histone H3 in brain tissue identifies MS-275 as a promising candidate drug in the treatment of malignant gliomas. 相似文献
95.
Angelika Gutenberg Martin D. Nischwitz Bastian Gunawan Christina Enders Klaus Jung Markus Bergmann Wolfgang Feiden Rupert Egensperger Kathy Keyvani Dietmar Stolke Ulrich Sure Henry W.S. Schroeder Rolf Warzok Ralf Schober Jürgen Meixensberger Werner Paulus Hansdetlef Wassmann Wolfgang Stummer Ingmar Blumcke Michael Buchfelder Frank K.H. van Landeghem Peter Vajkoczy Marlis Günther Jens Bedke Alf Giese Veit Rohde Wolfgang Brück Laszlo Füzesi Bjoern Sander 《Cancer genetics》2014,207(5):206-213
96.
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99.
Landgren S von Otter M Palmér MS Zetterström C Nilsson S Skoog I Gustafson DR Minthon L Wallin A Andreasen N Bogdanovic N Marcusson J Blennow K Zetterberg H Kettunen P 《Journal of neural transmission (Vienna, Austria : 1996)》2012,119(7):833-842
Alzheimer's disease (AD) is the most common neurodegenerative disease, and is clinically characterized by cognitive disturbances and the accumulation of the amyloid β (Aβ) peptides in plaques in the brain. Recent studies have shown the links between AD and the immediate-early gene Arc (activity-regulated cytoskeleton-associated protein), involved in synaptic plasticity and memory consolidation. For example, AD mouse models show a decreased expression of Arc mRNA in the brain. In additional, acute Aβ application to brain slices leads to a widespread ARC protein diffusion, unlike the normal defined localization to synapses. In this study, we investigated genetic variation in human ARC and the risk of developing AD. To this end, we genotyped 713 subjects diagnosed with AD and 841 controls without dementia. ARC was sequenced in a group of healthy individuals, and seven previously known SNPs and three novel SNPs were identified. Two of the newly found SNPs were intronic and one, +2852(G/A), was located in the 3'UTR. Three tag SNPs were selected, including the novel SNP +2852(G/A), to relate to risk of AD, Mini Mental State Examination (MMSE) scores and cerebrospinal fluid (CSF) biomarker levels of total tau (T-tau), hyperphosphorylated tau181 (P-tau(181)) and Aβ(1-42). The AA genotype of the newly found 3'-UTR SNP +2852(A/G), was associated with a decreased risk of AD (p (c)?=?0.005; OR?=?0.74; 95?% CI: 0.61-0.89). No associations of single SNPs or haplotypes with MMSE score or CSF biomarkers were found. Here we report a novel ARC SNP associated with a reduced risk of developing AD. To our knowledge, this is the first study associating a gene variant of ARC with any disease. The location of the SNP within the 3'UTR indicates that dendritic targeting of ARC mRNA could be involved in the molecular mechanisms underlying this protective function. However, further investigation of the importance of this SNP for ARC function, ARC processing and the pathology of AD is needed. 相似文献
100.
Gustafson DR B?ckman K Lissner L Carlsson L Waern M Ostling S Guo X Bengtsson C Skoog I 《Alzheimer's & dementia》2012,8(4):272-277
BackgroundWe have shown that high mid-life central adiposity may increase the risk for dementia after 32 years. Leptin, an adipose tissue hormone, is correlated with adiposity measures and may contribute to a better etiological understanding of the relationship between high adiposity and dementia. We explored the relationship between serum leptin in mid-life and dementia, which is a late-life outcome.MethodsA longitudinal cohort study, the Prospective Population Study of Women, in Gothenburg, Sweden, includes a representative sample of 1462 women followed from mid-life ages of 38 to 60 years to late-life ages of 70 to 92 years. Women were examined in 1968, 1974, 1980, 1992, and 2000 using neuropsychiatric, anthropometric, clinical, and other measurements. Serum leptin was measured on samples collected at the 1968 baseline examination, after storage at −20°C for 29 years. Cox proportional hazards regression models estimated incident dementia risk by baseline leptin. Logistic regression models related leptin levels to dementia among surviving participants 32 years later. All models were adjusted for multiple potential confounders.ResultsMid-life leptin was not related to dementia risk using Cox or logistic regression models. This was observed despite positive baseline correlations between leptin and adiposity measures, and given our previous report of high mid-life waist-to-hip ratio being related to a twofold higher dementia risk.ConclusionsLeptin is not a mid-life marker of late-life dementia risk in this population sample of Swedish women born between 1908 and 1930. 相似文献