全文获取类型
收费全文 | 1626篇 |
免费 | 80篇 |
国内免费 | 56篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 76篇 |
妇产科学 | 15篇 |
基础医学 | 195篇 |
口腔科学 | 29篇 |
临床医学 | 180篇 |
内科学 | 443篇 |
皮肤病学 | 61篇 |
神经病学 | 103篇 |
特种医学 | 302篇 |
外科学 | 103篇 |
综合类 | 27篇 |
预防医学 | 69篇 |
眼科学 | 6篇 |
药学 | 82篇 |
中国医学 | 3篇 |
肿瘤学 | 65篇 |
出版年
2023年 | 10篇 |
2022年 | 7篇 |
2021年 | 23篇 |
2020年 | 13篇 |
2019年 | 28篇 |
2018年 | 34篇 |
2017年 | 8篇 |
2016年 | 11篇 |
2015年 | 24篇 |
2014年 | 26篇 |
2013年 | 54篇 |
2012年 | 49篇 |
2011年 | 39篇 |
2010年 | 60篇 |
2009年 | 74篇 |
2008年 | 48篇 |
2007年 | 74篇 |
2006年 | 46篇 |
2005年 | 43篇 |
2004年 | 33篇 |
2003年 | 36篇 |
2002年 | 30篇 |
2001年 | 30篇 |
2000年 | 29篇 |
1999年 | 33篇 |
1998年 | 77篇 |
1997年 | 88篇 |
1996年 | 106篇 |
1995年 | 64篇 |
1994年 | 59篇 |
1993年 | 53篇 |
1992年 | 25篇 |
1991年 | 26篇 |
1990年 | 31篇 |
1989年 | 44篇 |
1988年 | 43篇 |
1987年 | 42篇 |
1986年 | 55篇 |
1985年 | 43篇 |
1984年 | 10篇 |
1983年 | 15篇 |
1982年 | 14篇 |
1981年 | 10篇 |
1980年 | 13篇 |
1979年 | 8篇 |
1978年 | 14篇 |
1977年 | 11篇 |
1976年 | 14篇 |
1975年 | 13篇 |
1974年 | 6篇 |
排序方式: 共有1762条查询结果,搜索用时 15 毫秒
81.
BO Motayo PA Akinduti FA Adeyakinu PO Okerentugba JC Nwanze CC Onoh HC Innocent-Adiele IO Okonko 《African health sciences》2013,13(4):1091-1097
Background
The increased reports of ESBL dissemination from various centres in south western, Nigeria and the recent emergence of carbapenem resistant bacteria prompted the conception of this study.Objectives
To demonstrate the relationship between high molecular weight plasmids and the expression of antibiotic multi-resistance including ESBL and carbapenemase.Methods
We investigated 97 isolates of selected organisms consisting of 67 E. coli and 30 Klebseilla spp for the presence of plasmids expressing ESBL including carbapenem-hydrolysing enzymes. Beta-lactamase was determined using acidometric method, while ESBL and carbapenemase activity was determined using the double-disk diffusion test as well as the Modified Hodge test (MHT). Plasmid profiles of ESBL and carbapenemase positive isolates were determined according to standard protocols.Results
An ESBL prevalence rate of 21.6% and carbapenem- resistance rate of 9.3% was recorded. Antibiotic susceptibility profile of ESBL isolates showed 100.0% resistance against Amoxicillin, Cotrimoxazole and Erythromycin. Moderate susceptibility was recorded against the Quinolone class of antibiotics; Meropenem remained the most active antibiotic against ESBL isolates with 62.5% against E. coli and 60% against K. pneumoniae. The plasmid profiles of our study isolates ranged from 11.8kbp to 35.5kbp.Conclusion
Due to the relationship between high molecular weight plasmids and multi-drug resistance, we hereby recommend regular molecular surveillance of this form in our study setting. 相似文献82.
83.
Andreas Zuckermann Shoei-Shen Wang Eric Epailly Markus J. Barten Vilborg Sigurdardottir Javier Segovia Shaida Varnous Fabio M. Turazza Luciano Potena Hans B. Lehmkuhl 《Transplantation reviews (Orlando, Fla.)》2013,27(3):76-84
The efficacy of everolimus with reduced cyclosporine in de novo heart transplant patients has been demonstrated convincingly in randomized studies. Moreover, everolimus-based immunosuppression in de novo heart transplant recipients has been shown in two randomized trials to reduce the increase in maximal intimal thickness based on intravascular ultrasound, indicating attenuation of cardiac allograft vasculopathy (CAV). Randomized trials of everolimus in de novo heart transplantation have also consistently shown reduced cytomegalovirus infection versus antimetabolite therapy. In maintenance heart transplantation, conversion from calcineurin inhibitors to everolimus has demonstrated a sustained improvement in renal function. In de novo patients, a renal benefit may only be achieved if there is an adequate reduction in exposure to calcineurin inhibitor therapy. Delayed introduction of everolimus may be appropriate in patients at high risk of wound healing complications, e.g. diabetic patients or patients with ventricular assist device. The current evidence base suggests that the most convincing reasons for use of everolimus from the time of heart transplantation are to slow the progression of CAV and to lower the risk of cytomegalovirus infection. A regimen of everolimus with reduced-exposure calcineurin inhibitor and steroids in de novo heart transplant patients represents a welcome addition to the therapeutic armamentarium. 相似文献
84.
P. Garrido M. De Blas G. Ronzoni I. Cordero M. Antón E. Giné A. Santos A. Del Arco G. Segovia F. Mora 《Journal of neural transmission (Vienna, Austria : 1996)》2013,120(5):829-843
The present study was designed to investigate the modulation of the stress responses by the environmental conditions and its putative neurobiological mechanisms. For that an integrative study on the effects of environmental enrichment and isolation housing on (1) the corticosterone, dopamine and acetylcholine responses to acute restraint stress in the prefrontal cortex (PFC) of the awake rat; (2) the mRNA levels of glucocorticoid receptors (GRs) in the PFC, and (3) the behavioral responses to stress, related to the PFC (habituation to a novel environment, spatial-working memory and inhibitory avoidance response) was performed. Male Wistar rats were maintained from 3 to 6 months of age in two different conditions: enriched (EC) or impoverished (IC). Animals were stereotaxically implanted with bilateral guide cannulae in the PFC to perform microdialysis experiments to evaluate the concentrations of corticosterone, dopamine and acetylcholine. EC animals showed lower increases of corticosterone and dopamine but not of acetylcholine than IC animals in the PFC in response to acute restraint stress (20 min). In the PFC, GR mRNA levels showed a trend towards an enhancement in EC animals. EC reduced the days to learn the spatial working memory task (radial-water maze). Spatial working memory, however, was not different between groups in either basal or stress conditions. Inhibitory avoidance response was reduced in EC rats. The changes produced by EC in the neurochemical, neuroendocrine and behavioral parameters evaluated suggest that EC rats could show a better coping during an acute stress challenge. 相似文献
85.
86.
JC Jiménez-Mendoza FE Rivera-López MF González-Lara RD Valdez-Echeverría GE Castro-Narro A Tore LF Uscanga-Domínguez C Moctezuma-Velázquez 《Annals of hepatology》2022,27(3):100684
Introduction and ObjectivesThe emergence of SARS-CoV-2, which causes the coronavirus disease (COVID-19) has caused a great impact on healthcare systems worldwide, including hepatitis B and C viruses screening and elimination programs. The high number of COVID-19 hospitalizations represent a great opportunity to screen patients for hepatitis B virus (HBV) and hepatitis C virus (HCV), which was the aim of this study.Material and MethodsCross-sectional, retrospective study performed between April 2020 and 20201 at a referral center in Mexico dedicated to the care of adults with severe/critical COVID-19. We retrieved clinical, demographic, and laboratory results from each patient´s medical records, including antibodies against HCV (anti-HCV), HBV surface antigen (HBsAg), antibodies against the HBV core antigen (anti-HBcAg), and antibodies against HBsAg (anti-HBsAg).ResultsOut of 3620 patients that were admitted to the hospital, 24 (0.66%), 4 (0.11%), and 72 (1.99%) tested positive for anti-HCV, HBsAg, and anti-HBcAg, respectively. Of all seronegative patients, 954 (27%) had undetectable anti-HBsAg and 401 (12%) had anti-HBsAg at protective levels. Blood transfusion was the most relevant risk factor. Only 9.7% of the anti-HBc positive, 25% of the HBsAg positive, and 52% of the anti-HCV positive were aware of their serological status.ConclusionsIn this study we found a prevalence of anti-HCV of 0.66%, HBsAg in 0.11%, and isolated anti-HBcAg in 1.99%. We also found that HBV vaccination coverage has been suboptimal and needs to be reinforced. This study gave us a trustworthy insight of the actual seroprevalence in Mexico, which can help provide feedback to the Hepatitis National Elimination Plan. 相似文献
87.
Joshua J. Cook Madeline Wei Benny Segovia Ludmila Cosio-Lima Jeffrey Simpson Scott Taylor Yunsuk Koh Sangho Kim Youngil Lee 《Annals of hepatology》2022,27(4):100709
Introduction and aimNon-alcoholic fatty liver disease (NAFLD) is one of the most common diseases in the United States. Metabolic distress (obese diabetes) is the main causative element of NAFLD. While there is no cure for NAFLD, endurance exercise (EEx) has emerged as a therapeutic strategy against NAFLD. However, mechanisms of EXE-induced hepatic protection especially in female subjects remain unidentified. Thus, the aim of the study is to examine molecular mechanisms of EXE-induced hepatic protection against diet-induced NAFLD in female mice.Material and methodsNine-week-old female C57BL/6J mice were randomly divided into three groups: normal-diet control group (CON, n=11); high-fat diet/high-fructose group (HFD/HF, n=11); and HFD/HF+EEx group (HFD/HF+EEx, n=11). The mice assigned to HFD/HF and HFD/HF+EEx groups were fed with HFD/HF for 12 weeks, after which the mice assigned to the EEx group began treadmill exercise for 12 weeks, with HFD/HF continued.ResultsEEx attenuated hepatic steatosis, reduced de novo lipogenesis (reduction in ATP-Citrate- Lyase and diacylglycerol-O-acyltransferase 1), and enhanced mitochondrial biogenesis and fatty-acid activation (oxidative phosphorylation enzymes and Acyl-CoA synthetase1). Also, EEx prevented upregulation of gluconeogenic proteins (glyceraldehyde-3-phosphate dehydrogenase, glucose-6-phosphatase, and phosphoenolpyruvate-carboxykinase1), premature senescence (suppression of p53, p22, and p16, tumor-necrosis-factor-α, and interleukin-1β, and oxidative stress), and autophagy deficiency. Furthermore, EXE reversed apoptosis arrest (cleaved cysteine-dependent-aspartate-directed protease3 and Poly-(ADP-ribose)-polymerase1).ConclusionEEx-mediated reparations of metabolic and redox imbalance (utilization of pentose phosphate pathway), and autophagy deficiency caused by metabolic distress critically contribute to preventing/delaying severe progression of NAFLD. Also, EEx-induced anti-senescence and cell turnover are crucial protective mechanisms against NAFLD. 相似文献
88.
Kaneshka Masdjedi MD Laurens JC van Zandvoort BSc Matthew M Balbi MD Rutger-Jan Nuis MD PhD Jeroen Wilschut MD Roberto Diletti MD PhD Peter P.T. de Jaegere MD PhD Felix Zijlstra MD PhD Nicolas M Van Mieghem MD PhD Joost Daemen MD PhD 《Catheterization and cardiovascular interventions》2021,98(4):671-677
89.
Marsh JC; Will AJ; Hows JM; Sartori P; Darbyshire PJ; Williamson PJ; Oscier DG; Dexter TM; Testa NG 《Blood》1992,79(12):3138-3144
We have used the long-term bone marrow culture (LTBMC) system to analyze hematopoiesis in three patients with dyskeratosis congenita (DC), two of whom had aplastic anemia, and the third had a normal blood count (apart from mild macrocytosis) and normal BM cellularity. Hematopoiesis was severely defective in all three patients, as measured by a low incidence of colony-forming cells and a low level of hematopoiesis in LTBMC. The function of the marrow stroma was normal in its ability to support the growth of hematopoietic progenitors from normal marrows seeded onto them in all three cases, but the generation of hematopoietic progenitors from patients marrow cells inoculated onto normal stromas was reduced, thus suggesting the defect to be of stem cell origin. The parents and unaffected brother of one of the families have also been studied in LTBMC and all showed normal hematopoietic and stromal cell function. From this study we speculate that there are some similarities between DC and the defect in the W/Wv mouse. 相似文献
90.
Mimicking natural evolution in metallo-beta-lactamases through second-shell ligand mutations
下载免费PDF全文
![点击此处可从《Proceedings of the National Academy of Sciences of the United States of America》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Tomatis PE Rasia RM Segovia L Vila AJ 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(39):13761-13766
Metallo-beta-lactamases (MBLs) represent the latest generation of beta-lactamases. The structural diversity and broad substrate profile of MBLs allow them to confer resistance to most beta-lactam antibiotics. To explore the evolutionary potential of these enzymes, we have subjected the Bacillus cereus MBL (BcII) to a directed evolution scheme, which resulted in an increased hydrolytic efficiency toward cephalexin. A systematic study of the hydrolytic profile, substrate binding, and active-site features of the evolved lactamase reveal that directed evolution has shaped the active site by means of remote mutations to better hydrolyze cephalosporins with small, uncharged C-3 substituents. One of these mutations is found in related enzymes from pathogenic bacteria and is responsible for the increase in that enzyme's hydrolytic profile. The mutations lowered the activation energy of the rate-limiting step rather than improved the affinity of the enzyme toward these substrates. The following conclusions can be made: (i) MBLs are able to expand their substrate spectrum without sacrificing their inherent hydrolytic capabilities; (ii) directed evolution is able to mimic mutations that occur in nature; (iii) the metal-ligand strength is tuned by second-shell mutations, thereby influencing the catalytic efficiency; and (iv) changes in the position of the second Zn(II) ion in MBLs affect the substrate positioning in the active site. Overall, these results show that the evolution of enzymatic catalysis can take place by remote mutations controlling reactivity. 相似文献