首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   26598篇
  免费   2926篇
  国内免费   1942篇
耳鼻咽喉   156篇
儿科学   301篇
妇产科学   278篇
基础医学   2897篇
口腔科学   565篇
临床医学   3597篇
内科学   3508篇
皮肤病学   312篇
神经病学   1248篇
特种医学   896篇
外国民族医学   12篇
外科学   2440篇
综合类   5249篇
现状与发展   7篇
一般理论   2篇
预防医学   2155篇
眼科学   558篇
药学   2933篇
  37篇
中国医学   2327篇
肿瘤学   1988篇
  2024年   163篇
  2023年   603篇
  2022年   1431篇
  2021年   1725篇
  2020年   1418篇
  2019年   1022篇
  2018年   1070篇
  2017年   1042篇
  2016年   888篇
  2015年   1281篇
  2014年   1562篇
  2013年   1384篇
  2012年   2001篇
  2011年   2066篇
  2010年   1379篇
  2009年   1132篇
  2008年   1184篇
  2007年   1285篇
  2006年   1124篇
  2005年   1014篇
  2004年   885篇
  2003年   1060篇
  2002年   959篇
  2001年   788篇
  2000年   523篇
  1999年   459篇
  1998年   288篇
  1997年   319篇
  1996年   229篇
  1995年   203篇
  1994年   160篇
  1993年   91篇
  1992年   166篇
  1991年   124篇
  1990年   77篇
  1989年   75篇
  1988年   62篇
  1987年   69篇
  1986年   45篇
  1985年   35篇
  1984年   29篇
  1983年   14篇
  1982年   10篇
  1981年   7篇
  1980年   4篇
  1979年   11篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
981.
982.
983.
984.
Dietary calcium influences the regulation of energy metabolism, and weight gain is attenuated by a high-calcium diet. S100A16 is a novel calcium-binding signaling protein of the EF-hand superfamily that promotes adipogenesis. This study aimed to investigate the effect of S100A16 on weight gain attenuation with a calcium-rich diet. An obese rat model was produced after feeding with a high-fat diet. Animals were randomly divided into 4 groups according to the diet provided over 8 weeks: normal diet group; high-fat, normal-calcium diet group; high-fat, high-calcium diet (HH) group; and high-fat, low-calcium diet group. Serum biochemistry was analyzed, and body weight and visceral fat pads were measured. Expression of S100A16 was assayed by Western blotting. Adipogenesis was detected by oil red O staining. Increases in body weight and visceral fat weight were attenuated in the HH group. High-calcium diets decreased the concentrations of serum total cholesterol and triglyceride. Expression of S100A16 decreased in the HH group. Using the 3T3-L1 preadipocyte model, it was observed that elevation of intracellular Ca(2+) via calcium ionophores led to the exclusion of S100A16 from the nucleus. Overexpression of S100A16 in 3T3-L1 preadipocytes enhanced adipogenesis, although a significant reduction in Akt phosphorylation was also detected. High-calcium diets were associated with a significant reduction in body weight gain. High-calcium diets may lead to nuclear exclusion of S100A16, which results in the inhibition of adipogenesis and enhanced insulin sensitivity.  相似文献   
985.
The epidemics of insulin resistance (IR) and type 2 diabetes (T2D) affect the first world as well as less-developed countries, and now affect children as well. Persistently elevated oxidative stress and inflammation (OS/Infl) precede these polygenic conditions. A hallmark of contemporary lifestyle is a preference for thermally processed nutrients, replete with pro-OS/Infl advanced glycation endproducts (AGEs), which enhance appetite and cause overnutrition. We propose that chronic ingestion of oral AGEs promotes IR and T2D. The mechanism(s) involved in these findings were assessed in four generations of C57BL6 mice fed isocaloric diets with or without AGEs [synthetic methyl-glyoxal-derivatives (MG+)]. F3/MG+ mice manifested increased adiposity and premature IR, marked by severe deficiency of anti-AGE advanced glycation receptor 1 (AGER1) and of survival factor sirtuin 1 (SIRT1) in white adipose tissue (WAT), skeletal muscle, and liver. Impaired 2-deoxy-glucose uptake was associated with marked changes in insulin receptor (InsR), IRS-1, IRS-2, Akt activation, and a macrophage and adipocyte shift to a pro-OS/inflammatory (M1) phenotype. These features were absent in F3/MG mice. MG stimulation of 3T3-L1 adipocytes led to suppressed AGER1 and SIRT1, and altered InsR, IRS-1, IRS-2 phosphorylation, and nuclear factor kappa-light chain enhancer of activated B cells (Nf-κB) p65 acetylation. Gene modulation revealed these effects to be coregulated by AGER1 and SIRT1. Thus, prolonged oral exposure to MG-AGEs can deplete host-defenses AGER1 and SIRT1, raise basal OS/Infl, and increase susceptibility to dysmetabolic IR. Because exposure to AGEs can be decreased, these insights provide an important framework for alleviating a major lifestyle-linked disease epidemic.  相似文献   
986.
Syndapin I (PACSIN 1) is a synaptically enriched membrane tubulating protein that plays important roles in activity-dependent bulk endocytosis and neuronal morphogenesis. While syndapin I is an in vitro phosphoprotein, it is not known to be phosphorylated in neurons. Here, we report the identification of two phosphorylation sites, S76 and T181, of syndapin I from nerve terminals. Both residues are located at the N-terminal helix-capping motifs (N-Cap) of different α-helices in the F-BAR domain, important for F-BAR homodimer curvature and dimer-dimer filament assembly, respectively. Phospho-mimetic mutations of these residues regulate lipid-binding and tubulation both in vitro and in cells. Neither phosphosite regulated syndapin I function in activity-dependent bulk endocytosis. Rather, T181 phosphorylation was developmentally regulated and inhibited syndapin I function in neuronal morphogenesis. This suggests a novel mechanism for phosphorylation control of an F-BAR function through the regulation of α-helix interactions and stability within the folded F-BAR domain.  相似文献   
987.
Na-ASP-2 is a major protein secreted by infective third-stage larvae (L3) of the human hookworm Necator americanus upon host entry. It was chosen as a lead vaccine candidate for its ability to elicit protective immune responses. However, clinical development of this antigen as a recombinant vaccine was halted because it caused allergic reactions among some of human volunteers previously infected with N.?americanus. To prevent IgE-mediated allergic reactions induced by Na-ASP-2 but keep its immunogenicity as a vaccine antigen, we designed and tested a genetically engineered fusion protein, Fcγ/Na-ASP-2, composed of full-length Na-ASP-2 and truncated human IgG Fcγ1 that targets the negative signalling receptor FcγRIIb expressed on pro-allergic cells. The chimeric recombinant Fcγ/Na-ASP-2 protein was expressed in Pichia pastoris and shared the similar antigenicity as native Na-ASP-2. Compared to Na-ASP-2, the chimeric fusion protein efficiently reduced the release of histamine in human basophils sensitized with anti-Na-ASP-2 IgE obtained from individuals living in a hookworm-endemic area. In dogs infected with canine hookworm, Fcγ/Na-ASP-2 resulted in significantly reduced immediate-type skin reactivity when injected intradermally compared with Na-ASP-2. Hamsters vaccinated with Fcγ/Na-ASP-2 formulated with Alhydrogel(?) produced specific IgG that recognized Na-ASP-2 and elicited similar protection level against N.?americanus L3 challenge as native Na-ASP-2.  相似文献   
988.
Left ventricular systolic dysfunction in patients with severe aortic stenosis (AS) is associated with poor outcome. This analysis was designed primarily to describe the clinical course of a large series of consecutive patients with severe AS and low ejection fraction (EF) (<40%) who, because of high surgical risk, were referred for transcatheter aortic valve implantation consideration. A cohort of 270 patients with severe AS and low EF (<40%) who were referred to participate in a clinical trial of transcatheter aortic valve implantation was studied. Clinical, hemodynamic, and periprocedural complications and follow-up mortality data were collected and compared between patients with low mean transvalvular gradients (≤40 mm Hg, n = 170 [63%]) and high transvalvular gradients (>40 mm Hg, n = 100 [37%]). Patients with low gradients were younger (mean age 79.8 ± 9.1 vs 83.8 ± 7.7 years, p <0.001) and had higher incidences of coronary artery disease and renal failure. Mean aortic valve area was larger (0.73 ± 0.23 vs 0.53 ± 0.18 cm(2), p <0.001), while mean EF (26.4 ± 6.9% vs 30.5% ± 6.6%, p <0.001), cardiac output (3.7 ± 1.1 vs 4.1 ± 1.3 L/min, p = 0.04), and cardiac index (1.9 ± 0.5 vs 2.1 ± 0.6 L/min/m(2), p = 0.04) were lower in patients with lower gradients compared to those with higher gradients, respectively. Mortality was higher in patients with low gradients (53.8%) at a mean follow-up of 151 days compared to those with high gradients (41%) at a mean follow-up of 256 days (p = 0.01). In conclusion, patients with severe AS and low EF with low transvalvular gradients are at higher risk for worse outcomes compared to patients with high transvalvular gradients. Surgery or transcatheter aortic valve implantation treatment and high baseline transvalvular gradient are associated with EF improvement.  相似文献   
989.
Data from randomized clinical trials have shown the safety and efficacy of the XIENCE V in selected populations. However, limited data are available comparing the XIENCE V to the first-generation CYPHER sirolimus-eluting stent. This study aimed to assess the long-term safety and clinical efficacy of the XIENCE V everolimus-eluting stent compared to first-generation stents in an unselected patient population. This retrospective analysis included 6,069 patients treated with CYPHER, TAXUS, and XIENCE stents from 2003 to 2009 at our institution. The patients were followed up for ≥1 year after the index procedure. The baseline characteristics were generally comparable among the 3 groups, with the exception of a significantly greater prevalence of diabetes mellitus, systemic hypertension, and a history of angioplasty and coronary bypass surgery among the XIENCE patients. The XIENCE patients also had a twofold greater rate of type C lesions. One-year follow-up data were available for 82% of the patients. The 1-year major adverse cardiovascular events rate was 9.3% for the XIENCE stent versus 9.8% for the CYPHER stent and 11.5% for the TAXUS stent (p = 0.11). Mortality was lower in the XIENCE group than in the CYPHER and TAXUS groups (3.6% vs 4.9% vs 7.2%, respectively, p <0.001), and target lesion revascularization was similar (5.9% vs 5.2% vs 5.6%, respectively; p = 0.34). Stent thrombosis was lower in the XIENCE patients (0.2% vs 1.2% vs 0.7%, p = 0.007). In conclusion, in a contemporary United States clinical practice with an unselected patient population, use of the XIENCE V stent was associated with an improved safety profile and reduction of all-cause mortality and stent thrombosis compared to first-generation drug-eluting stents. The XIENCE V failed to demonstrate superiority for overall major adverse cardiovascular events, Q-wave myocardial infarction, and revascularization rates.  相似文献   
990.
IntroductionThe objective is to investigate the influence of ghrelin administration on both the insulin secretion and the expression of ATP-sensitive K+ channels in islet.MethodsGhrelin and [D-Lys3] growth hormone releasing peptide-6 were administered via intraperitoneal injection in Wistar rats at the doses 10 and 10 μmol/kg/d for 2 weeks, respectively. Then glucose tolerance tests were performed and plasma insulin concentrations were measured. Islets were isolated for insulin release experiments. Single β cells were isolated for electrophysiological experiments. Determination of the Kir6.2 and SUR1 mRNA and protein expression levels in islets was performed by polymerase chain reaction and western blotting.ResultsIntraperitoneal administration of exogenous ghrelin significantly (P < 0.05) increased blood glucose concentrations, attenuated insulin responses during glucose tolerance tests, reduced insulin release from the isolated islets induced by 11.1 and 16.7 mmol/L glucose, hyperpolarized the resting membrane potential and increased the Kir6.2 mRNA and protein expression levels. In contrast, counteraction of ghrelin by intraperitoneal injection of [D-Lys3] growth hormone releasing peptide-6 significantly (P < 0.05) attenuated the aforementioned changes. SUR1 expression levels were not altered in this study.ConclusionsGhrelin via pancreatic growth hormone secretagogue receptor up-regulates the Kir6.2 expression in islet by hyperpolarizing the resting membrane potential which results in the inhibition of insulin release.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号