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   108434篇
  免费   8951篇
  国内免费   4999篇
耳鼻咽喉   740篇
儿科学   2198篇
妇产科学   1941篇
基础医学   12917篇
口腔科学   2517篇
临床医学   10759篇
内科学   17083篇
皮肤病学   1474篇
神经病学   9379篇
特种医学   2134篇
外国民族医学   31篇
外科学   9188篇
综合类   17730篇
现状与发展   13篇
预防医学   9281篇
眼科学   2862篇
药学   10312篇
  32篇
中国医学   3622篇
肿瘤学   8171篇
  2024年   289篇
  2023年   1313篇
  2022年   2937篇
  2021年   3851篇
  2020年   3426篇
  2019年   3119篇
  2018年   3090篇
  2017年   3512篇
  2016年   3830篇
  2015年   3769篇
  2014年   6793篇
  2013年   7465篇
  2012年   6898篇
  2011年   7749篇
  2010年   6445篇
  2009年   6072篇
  2008年   6322篇
  2007年   6251篇
  2006年   5641篇
  2005年   4935篇
  2004年   4189篇
  2003年   3624篇
  2002年   2990篇
  2001年   2564篇
  2000年   2187篇
  1999年   1841篇
  1998年   1585篇
  1997年   1370篇
  1996年   1224篇
  1995年   1108篇
  1994年   930篇
  1993年   721篇
  1992年   646篇
  1991年   501篇
  1990年   457篇
  1989年   350篇
  1988年   295篇
  1987年   239篇
  1986年   194篇
  1985年   311篇
  1984年   254篇
  1983年   157篇
  1982年   224篇
  1981年   142篇
  1980年   151篇
  1979年   97篇
  1978年   73篇
  1977年   59篇
  1976年   55篇
  1975年   45篇
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
1.
2.
《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   
3.
目的:分析腹腔镜胆囊切除术的临床疗效,分析其对血清应激指标的影响。方法:将160例来我院行胆囊切除术的患者随机分为两组,对照组和观察组各80例。对照组采用开腹胆囊切除术,观察组则采用腹腔镜胆囊切除术。比较两组间手术时间、术中出血量、肠功能恢复时间以及住院天数差异,比较治疗前后两组患者间血清应激相关指标皮质醇(COR)、去甲肾上腺素(NE)、促肾上腺皮质激素(ACTH)、多巴胺(DA)以及胰岛素(INS)、三碘甲状腺原氨酸(T3)、甲状腺素(T4)、促甲状腺激素释放激素(TSH)水平差异。结果:观察组患者手术时间、术中出血量、肠功能恢复时间以及住院天数均显著少于对照组(P<0.05)。血清COR、NE、ACTH、DA和INS、T3水平在围手术期均发生了显著变化,各项指标均在胆囊分离时就明显升高,术后24 h开始下降(P<0.05);术后观察组上述指标均显著低于对照组(P<0.05)。结论:腹腔镜胆囊切除术对机体应激反应影响小于开腹手术,更利于患者术后康复。  相似文献   
4.
BackgroundBurnout in teachers has been linked to decreased effectiveness as educators, and suboptimal interactions with students. The purpose of this pilot study was to assess the outcomes of a brief Stress Management and Resiliency Training (SMART) program for public school staff.Materials and methodsThis single-arm, prospective trial involved an investigation of the effects of a brief SMART program on participant stress, anxiety, resilience, gratitude, happiness, life satisfaction, and quality of life (QOL).ResultsSignificant improvements were noted in participant anxiety (P < 0.001), stress (P = 0.003), gratitude (P = 0.001), happiness (P < 0.001), life satisfaction (P < 0.001), and QOL (P < 0.001). Most participants reported that the skills learned positively affected interactions with students (77.2%) and coworkers (72.2%).ConclusionsThe SMART program showed promising effectiveness for improving anxiety, stress, gratitude, happiness, life satisfaction and QOL. Given the prevalence and impact of teacher burnout, larger, controlled trials and broader dissemination of the intervention are warranted.  相似文献   
5.
Accurately predicting the hepatic clearance of compounds using in vitro to in vivo extrapolation (IVIVE) is crucial within the pharmaceutical industry. However, several groups have recently highlighted the serious error in the process. Although empirical or regression-based scaling factors may be used to mitigate the common underprediction, they provide unsatisfying solutions because the reasoning behind the underlying error has yet to be determined. One previously noted trend was intrinsic clearance-dependent underprediction, highlighting the limitations of current in vitro systems. When applying these generated in vitro intrinsic clearance values during drug development and making first-in-human dose predictions for new chemical entities though, hepatic clearance is the parameter that must be estimated using a model of hepatic disposition, such as the well-stirred model. Here, we examine error across hepatic clearance ranges and find a similar hepatic clearance-dependent trend, with high clearance compounds not predicted to be so, demonstrating another gap in the field.  相似文献   
6.
目的探讨补骨脂素抗增生性瘢痕的作用机制。方法体外培养成纤维细胞,按随机数字表法分为正常组(培养正常成纤维细胞)、瘢痕组(培养增生性瘢痕成纤维细胞)、TGF-β1组(10 ng/ml TGF-β1处理增生性瘢痕成纤维细胞5 min^12 h)、Smurf2 RNA干扰组[Smad泛素化调节因子2(Smad ubiquitin regulatory factor2,Smurf2)siRNA转染增生性瘢痕成纤维细胞72 h]、补骨脂素组(10μmol/L补骨脂素处理增生性瘢痕成纤维细胞继续培养72 h)、补骨脂素+TGF-β1组(增生性瘢痕成纤维细胞加入补骨脂素培养72 h后加入TGF-β1培养6 h)。采用Western blot法检测Smurf2、α-平滑肌肌动蛋白(α-actin SMA,α-SMA)蛋白表达;RT-PCR法检测Ⅰ型胶原蛋白mRNA表达;ELISA法检测TGF-β1蛋白分泌。结果与正常组比较,瘢痕组Smurf2蛋白[(0.83±0.08)比(0.38±0.07)]表达增加(P<0.05);与瘢痕组比较,Smurf2 RNA干扰组TGF-β1[(2.2±0.18)比(4.2±0.47)]表达降低(P<0.05);TGF-β1组Smurf2[(0.71±0.06)比(0.42±0.04)]、α-SMA[(1.42±0.12)比(0.91±0.09)]蛋白表达增加(P<0.05),Ⅰ型胶原蛋白mRNA[(0.72±0.09)比(0.41±0.07)]表达增加(P<0.05);补骨脂素组Smurf2[(0.05±0.01)比(0.42±0.04)]、α-SMA[(0.71±0.07)比(0.91±0.09)]蛋白表达降低(P<0.05),Ⅰ型胶原蛋白mRNA表达[(0.12±0.04)比(0.41±0.07)]降低(P<0.05)。结论补骨脂素可能通过TGF-β1/Smurf2信号通路抑制α-SMA蛋白表达,从而降低Ⅰ型胶原蛋白表达,起到抑制瘢痕形成的作用。  相似文献   
7.
Introduction Patients with cystic fibrosis (CF) are known to be at risk for early osteoporosis, and the mechanisms that mediate bone loss are still being delineated. The aim of the present investigation was to investigate if a correlation exists in these patients between skeletal measurements by dual-energy x-ray absorptiometry (DXA) and two anabolic factors, dehydroepiandrosterone (DHEA) and insulin-like growth factor I (IGF-I), and proresorptive factors such as the cytokines interleukin-1β, tumor necrosis factor α, and interleukin-6. Methods We studied 32 outpatients (18 females; mean age: 26.2 ± 7.9 years) at a tertiary care medical center. The subjects had venous samples obtained, underwent anthropometric and bone mineral density (BMD) measurements, and completed a health survey. Serum IGF-I concentrations were below the age-adjusted mean in 78% of the participants, and DHEA sulfate (DHEAS) concentrations were low in 72%. Serum concentrations of all cytokines were on the low side of normal; nonetheless, there was a modest inverse correlation between IL-1β and BMD at all sites. Results In univariate analyses, IGF-I and DHEAS were significant correlates of BMD or bone mineral content. In final multivariate models controlling for anthropometric and other variables of relevance to bone density, only IGF-I was identified as a significant independent skeletal predictor. While alterations in DHEAS, IGF-I, and specific cytokines may contribute to skeletal deficits in patients with CF, of these factors a low IGF-I concentration appears to be most strongly correlated with BMD. Conclusions These findings may have therapeutic implications for enhancing bone density in these patients.  相似文献   
8.
表皮生长因子对牛眼小梁细胞c—fos基因表达的诱导   总被引:4,自引:0,他引:4  
目的研究表皮生长因子(epidermalgrowthfactor,EGF)对小梁细胞的作用。方法应用分子杂交技术研究EGF对体外培养的牛眼小梁细胞c-fos基因表达的诱导和3H胸腺核苷酸(3H-thymidineincorparation,3H-TdR)掺入法观察细胞DNA的合成。结果小梁细胞的3H-TdR掺入率随着EGF浓度不同而变化,浓度为20~150ng/ml时,细胞掺入率随浓度增加升高(P<0.01)。与对照组相比,EGF刺激停止生长的小梁细胞0.5小时后,c-fos基因开始表达,1小时后达高峰,至2小时后消失。不同浓度EGF刺激小梁细胞1小时后,c-fos基因表达呈浓度依赖性。结论实验结果表明EGF刺激小梁细胞增殖或进入生长状态,可能与c-fos基因产物的信号传递作用有关。  相似文献   
9.
提要本研究是在大鼠VD_3+Nicotine引起的心血管钙超载模型上观察心钠素(ANF)治疗(10ug ·kg~-1/d),对钙超载的影响。结果发现,钙超载组动物主动脉、心肌组织钙含量较对照组分别增高24倍(54.4±2.2vs 2.3±0.04fumol/gww)和9倍(16.9±2.1vs1.8±0.1umol/gww)。ANF治疗能显著抑制钙超载的发生,主动脉和心肌组织钙含量较钙超载组分别降低92%(3.8±0.4 umol/gww)和66%(5.6±0.6umol/gww)。离体滋流的钙超载血管环较对照组对去甲肾上腺素收缩反应增强;对乙酰胆碱舒张反应减弱,对硝普钠舒张反应无影响。ANF能显著改善钙超载所致的血管反应性障碍。实验结果表明,ANF具有显著的防治心血管钙超载的作用。  相似文献   
10.
While the benefits of training manuals can hardly be questioned, they are exceedingly limited in reducing variability attributed to the "therapist factor." We propose that manuals provide a useful outline of the general principles of a therapeutic approach, but can only reduce therapist variability at the expense of other essential therapeutic phenomena. Manuals cannot adequately convey, for example, how the effective therapist functions as a model of adult living and as a person who provides guidance. We suggest that such an experience cannot readily be packaged in manualized form, though manuals may serve as a useful beginning. Recommendations for therapist manualized training include greater attention to the subtleties of human relationships and adequately conveying that any technique is effective only when catalysed by a living, relational process.  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