全文获取类型
收费全文 | 230622篇 |
免费 | 19965篇 |
国内免费 | 7593篇 |
专业分类
耳鼻咽喉 | 1379篇 |
儿科学 | 4542篇 |
妇产科学 | 2195篇 |
基础医学 | 42119篇 |
口腔科学 | 3828篇 |
临床医学 | 21335篇 |
内科学 | 38122篇 |
皮肤病学 | 3173篇 |
神经病学 | 11464篇 |
特种医学 | 6271篇 |
外国民族医学 | 32篇 |
外科学 | 18283篇 |
综合类 | 32981篇 |
现状与发展 | 27篇 |
一般理论 | 25篇 |
预防医学 | 14494篇 |
眼科学 | 5214篇 |
药学 | 23694篇 |
27篇 | |
中国医学 | 10318篇 |
肿瘤学 | 18657篇 |
出版年
2023年 | 2654篇 |
2022年 | 4210篇 |
2021年 | 7752篇 |
2020年 | 6925篇 |
2019年 | 7971篇 |
2018年 | 7914篇 |
2017年 | 7655篇 |
2016年 | 7693篇 |
2015年 | 8122篇 |
2014年 | 12498篇 |
2013年 | 14309篇 |
2012年 | 11608篇 |
2011年 | 13300篇 |
2010年 | 11089篇 |
2009年 | 10770篇 |
2008年 | 10869篇 |
2007年 | 12047篇 |
2006年 | 10982篇 |
2005年 | 10558篇 |
2004年 | 9373篇 |
2003年 | 8376篇 |
2002年 | 6405篇 |
2001年 | 6243篇 |
2000年 | 5140篇 |
1999年 | 4705篇 |
1998年 | 3710篇 |
1997年 | 3413篇 |
1996年 | 3267篇 |
1995年 | 3221篇 |
1994年 | 2896篇 |
1993年 | 2523篇 |
1992年 | 2033篇 |
1991年 | 1717篇 |
1990年 | 1452篇 |
1989年 | 1334篇 |
1988年 | 1200篇 |
1987年 | 933篇 |
1986年 | 739篇 |
1985年 | 1241篇 |
1984年 | 1400篇 |
1983年 | 975篇 |
1982年 | 1077篇 |
1981年 | 950篇 |
1980年 | 835篇 |
1979年 | 732篇 |
1978年 | 594篇 |
1977年 | 475篇 |
1976年 | 565篇 |
1975年 | 452篇 |
1974年 | 365篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
91.
Denise Lee Marcella D. Walker Hsin Yi Chen John A. Chabot James A. Lee Jennifer H. Kuo 《Surgery》2019,165(1):107-113
Background
Bone mineral density (BMD) has been found to improve after parathyroidectomy (PTX) in patients with primary hyperparathyroidism. There are few data on the effect of PTX on BMD in normocalcemic and normohormonal primary hyperparathyroidism.Methods
A retrospective analysis of 92 primary hyperparathyroidism patients who underwent PTX between 2004 and 2012 with pre- and post-PTX dual-energy x-ray absorptiometry was performed. Within-person changes in BMD pre- and post-PTX were analyzed using log linear mixed models, stratified by biochemical status.Results
Bone mineral density increased post-PTX in the whole cohort at the lumbar spine (+2.5%), femoral neck (+2.1%), and total hip (+1.9%) and decreased at the one-third radius (–0.9%). On comparison of BMD changes by profile, BMD increased in those with the typical profile at the lumbar spine (3.2%), femoral neck (2.9%), and total hip (2.9%) but declined at the one-third radius (–1.5%). In contrast, BMD improved only at the femoral neck (4.3%) in the normohormonal group and did not change at any site in the normocalcemic group. The typical group had a greater increase in BMD over time at the femoral neck and total hip compared with normocalcemic patients.Conclusion
Our results indicate that the skeletal benefit of PTX was attenuated in normocalcemic and normohormonal patients, suggesting that skeletal changes after PTX may depend on biochemical profile. 相似文献92.
《Vaccine》2019,37(31):4382-4391
Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8+ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα+ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice. 相似文献
93.
Non‐melanoma skin cancer frequently results from chronic exposure to ultraviolet (UV) irradiation. UV‐induced DNA damage activates cell cycle arrest checkpoints through degradation of the cyclin‐dependent kinase activators, the cell division cycle 25 (CDC25) phosphatases. We previously reported increased CDC25A in nonmelanoma skin cancer, but CDC25B and CDC25C had not been previously examined. Consequently, we hypothesized that increased expression of CDC25B and CDC25C increases tumor cell proliferation and skin tumor growth. We found that CDC25B and CDC25C were increased in mouse and human skin cancers. CDC25B was primarily cytoplasmic in skin and skin tumors and was significantly increased in the squamous cell carcinoma (SCC), while CDC25C was mostly nuclear in the skin, with an increased cytoplasmic signal in the premalignant and malignant tumors. Surprisingly, forced expression of CDC25B or CDC25C in cultured SCC cells did not affect proliferation, but instead suppressed apoptosis, while CDC25C silencing increased apoptosis without impacting proliferation. Targeting CDC25C to the nucleus via mutation of its nuclear export sequence, however, increased proliferation in SCC cells. Overexpression of CDC25C in the nuclear compartment did not hinder the ability of CDC25C to suppress apoptosis, neither did mutation of sites necessary for its interaction with 14‐3‐3 proteins. Analysis of apoptotic signaling pathways revealed that CDC25C increased activating phosphorylation of Akt on Ser473, increased inhibitory phosphorylation of proapoptotic BAD on Ser136, and increased the survival protein Survivin. Silencing of CDC25C significantly reduced Survivin levels. Taken together, these data suggest that increased expression of CDC25B or CDC25C are mechanisms by which skin cancers evade apoptotic cell death. 相似文献
94.
目的:建立大黄特征化学成分和抗氧化活性相关联的二维指纹图谱,研究大黄抗氧化活性物质。方法:利用高效液相多检测器联用的抗氧化活性成分在线检测体系,对大黄中化学成分进行检测,共鉴定出大黄中化学成分15种;其中8种具有抗氧化活性;然后采用清除效率为指标对各活性成分的抗氧化活性进行评价。结果:结果发现化合物葡萄糖紫丁香酸、腺嘌呤、没食子酸、儿茶素或表儿茶素、双花母草素、2-O-桂皮酰-没食子酰葡萄糖等具有较强的清除ABTS·+的活性,而蒽醌类成分对ABTS·+的清除作用较弱。结论:采用HPLC-ABTS-DAD-Q-TOF/MS对大黄中的抗氧化活性成分进行快速分析鉴定,初步阐明大黄在抗氧化环节起作用的效应物质。 相似文献
95.
Could non-HDL-cholesterol be a better marker of atherogenic dyslipidemia in obstructive sleep apnea?
《Sleep medicine》2021
Background/objectiveObstructive sleep apnea (OSA) is independently associated with dyslipidemia, a surrogate marker of atherosclerosis. Low-density lipoprotein (LDL)-cholesterol is accepted as a major independent risk factor for cardiovascular disease. However, non-high-density lipoprotein (HDL)-cholesterol is a better marker of atherogenic dyslipidemia and recommended as a target of lipid lowering therapy. We aimed to assess the prevalence of atherogenic dyslipidemia, and relationship between OSA severity and serum LDL-cholesterol and non-HDL cholesterol levels in OSA patients.MethodsWe retrospectively evaluated treatment naïve 2361 subjects admitted to the sleep laboratory of a university hospital for polysomnography. All subjects’ lipid profile including total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and non-HDL-cholesterol were measured.ResultsOut of 2361 patients (mean age 49.6 ± 11.9 years; 68.9% male, apnea-hypopnea index 36.6 ± 28.4/h), 185 (7.8%) had no OSA and 2176 (92.2%) had OSA. Atherogenic dyslipidemia prevalence was high (57–66%) in OSA patients, and especially increased in severe OSA compared to other groups (p < 0.05). Though total and LDL-cholesterol did not differ between those with and without OSA, non-HDL-cholesterol (p = 0.020), and triglycerides (p = 0.001) were higher and HDL-cholesterol levels (p = 0.018) were lower in OSA patients than non-OSA. Non-HDL-cholesterol was significantly correlated with OSA severity (p < 0.001) and hypoxia parameters (p < 0.01), whereas LDL-cholesterol showed no correlation.ConclusionsAtherogenic dyslipidemia is highly prevalent and non-HDL-cholesterol levels are significantly increased, predominantly in severe OSA patients. Non-HDL-cholesterol but not LDL-cholesterol, is significantly correlated with OSA severity and hypoxia parameters. Therefore, it could be better to use non-HDL-cholesterol, which is a guideline recommended target of lipid therapy, as a marker of atherosclerotic cardiovascular risk in OSA patients. 相似文献
96.
97.
《Saudi Pharmaceutical Journal》2022,30(6):669-678
BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction. 相似文献
98.
Alexander C. Egbe Rosalyn Adigun Vidhu Anand Collin P. West Victor M. Montori Hassan M. Murad Emmanuel Akintoye Karim Osman Heidi M. Connolly 《The Canadian journal of cardiology》2019,35(12):1784-1790
BackgroundAlthough there are robust data about the pathophysiology and prognostic implications of left ventricular (LV) systolic dysfunction in patients with acquired heart disease, similar prognostic data about LV systolic dysfunction are sparse in the tetralogy of Fallot (TOF) population. The purpose of this study was to perform a meta-analysis of all studies that assessed the relationship between LV ejection fraction (LVEF) and cardiovascular adverse events (CAEs) defined as death, aborted sudden death, or sustained ventricular tachycardia.MethodsWe used random-effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsOf the 1,809 citations, 7 studies with 2,854 patients (age 28 ± 4 years) were included. During 5.6 ± 3.4 years' follow-up, there were 82 deaths, 17 aborted sudden cardiac deaths, and 56 sustained ventricular tachycardia events. Overall, CAEs occurred in 5.1% (144 patients). As a continuous variable, LVEF was a predictor of CAE (HR 1.29, 95% CI, 1.09-1.53, P = 0.001) per 5% decrease in LVEF. Similarly, LVEF < 40% was also a predictor of CAE (HR 3.22, 95% CI, 2.16-4.80, P < 0.001).ConclusionsLV systolic dysfunction was an independent predictor of CAE, and we observed a 30% increase in the risk of CAE for every 5% decrease in LVEF, and a 3-fold increase in the risk of CAE in patients with LVEF <40% compared with other patients. These findings underscore the importance of incorporating LV systolic function in clinical risk stratification of patients with TOF and the need to explore new treatment options to address this problem. 相似文献
99.
Marta López-Fauqued Laura Campora Frédérique Delannois Mohamed El Idrissi Lidia Oostvogels Ferdinandus J. De Looze Javier Diez-Domingo Thomas C. Heineman Himal Lal Janet E. McElhaney Shelly A. McNeil Wilfred Yeo Fernanda Tavares-Da-Silva 《Vaccine》2019,37(18):2482-2493
Background
The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.Methods
Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30?days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12?months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period.Results
Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race.Conclusions
No safety concerns arose, supporting the favorable benefit-risk profile of RZV. 相似文献100.
目的探讨喉癌患者血小板表面血小板膜糖蛋白Ⅱb/Ⅲa纤维蛋白原受体(PAC-1)、血小板P-选择素(CD62P)阳性表达率以及与患者临床病理特征和复发的关系。方法选取2014年1月~2015年12月间在我院耳鼻喉科手术治疗的116例喉癌患者,随访≥2年,并选取同期在我院体检的健康人群60例为对照组,采用流式细胞仪检测法检测外周血PAC-1和CD62P阳性率,并分析与临床病理特征、复发的关系。结果喉癌患者PAC-1和CD62P阳性表达率分别为(17.82±1.76)%和(22.87±3.13)%,明显高于健康人群(P<0.05);而且在喉癌患者PAC-1表达和CD62P表达呈正相关性(r=0.238,P<0.05)。T3-T4分期或N2-N3分期患者PAC-1和CD62P阳性表达率高于T1-T2分期或N0-N1分期患者(P<0.05)。另外远处转移组PAC-1和CD62P阳性表达率高于未发生转移组(P<0.05);随访期间有24例患者复发,复发率为20.69%。复发喉癌患者PAC-1、CD62P阳性表达率分别为(17.02±0.85)%和(21.84±1.17)%,明显高于未复发的喉癌患者(P<0.05)。经Logistics回归分析,PAC-1和CD62P是喉癌患者复发的独立危险因素(P<0.05)。结论PAC-1和CD62P阳性表达率与喉癌患者T分期、淋巴结转移和远处转移密切相关,同时可作为喉癌局部复发、区域淋巴结转移、远处转移的预测指标。 相似文献