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   8536篇
  免费   1266篇
  国内免费   3747篇
  2024年   105篇
  2023年   268篇
  2022年   377篇
  2021年   434篇
  2020年   420篇
  2019年   464篇
  2018年   290篇
  2017年   308篇
  2016年   320篇
  2015年   480篇
  2014年   672篇
  2013年   605篇
  2012年   826篇
  2011年   761篇
  2010年   636篇
  2009年   635篇
  2008年   691篇
  2007年   680篇
  2006年   611篇
  2005年   553篇
  2004年   414篇
  2003年   401篇
  2002年   335篇
  2001年   307篇
  2000年   313篇
  1999年   226篇
  1998年   116篇
  1997年   108篇
  1996年   60篇
  1995年   65篇
  1994年   45篇
  1993年   40篇
  1992年   76篇
  1991年   82篇
  1990年   73篇
  1989年   86篇
  1988年   54篇
  1987年   45篇
  1986年   57篇
  1985年   42篇
  1984年   32篇
  1983年   45篇
  1982年   44篇
  1981年   33篇
  1980年   16篇
  1979年   30篇
  1978年   34篇
  1977年   20篇
  1976年   21篇
  1974年   25篇
排序方式: 共有10000条查询结果,搜索用时 24 毫秒
991.
目的:探讨多系统萎缩(multiple system atrophy,MSA)患者的临床表现及神经影像学新特征(脑桥"十字征"和"壳核裂隙征")在MSA早期诊断中的临床意义。方法:回顾性分析21例临床诊断为多系统萎缩(MSA)患者的临床表现和头部MRI资料。结果:21例MSA患者中,Shy-Drager综合征(MSA-A)9例,早期临床表现为体位性低血压,泌尿生殖功能障碍,头部MRI检查脑桥"壳核裂隙征"和"十字征"为Ⅰ期;橄榄体脑桥小脑萎缩(MSA-C)5例,3例发病后1年头部MRI脑桥"十字征"达Ⅱ期;"壳核裂隙征"为Ⅰ期,2例发病后3年头部MRI脑桥"十字征"达Ⅳ期。黑质纹状体变性(MSA-P)7例:早期临床均有运动迟缓、震颤等表现,3例发病后1年脑桥"十字征"Ⅰ期,"壳核裂隙征"Ⅲ期;3例发病后2年脑桥"十字征"Ⅰ期,"壳核裂隙征"Ⅰ期;另1例发病后9月脑桥"十字征"Ⅰ期",壳核裂隙征"Ⅱ期。结论:认为临床表现与头部MRI检查显示的新的影像学特征结合有助于MSA早期诊断。  相似文献   
992.
目的:探讨健康教育及心理护理对突发性耳聋患者的负性情绪及患者满意度的影响。方法:将120例突发性耳聋患者随机分入对照组与观察组,每组各60例。给予对照组患者常规护理措施,观察组患者接受系统的健康教育及个体化的心理护理。采用焦虑自评量表(SAS)以及抑郁自评量表(SDS)对两组干预前后负性情绪进行评估,同时比较两组临床疗效及患者满意度。结果:治疗后观察组SAS评分及SDS评分显著低于对照组(P<0.05);观察组与对照组治疗总有效率分别为78.3%和61.7%,差别具有统计学意义(P<0.05);治疗后观察组患者满意率显著高于对照组(95.0%vs 81.7%,P<0.05)。结论:对突发性耳聋患者采取系统的健康教育,同时给予个体化的心理干预,可显著减轻患者的负性情绪,提高临床疗效及患者满意度。  相似文献   
993.
目的:探讨关节镜下有限清理术治疗膝关节骨性关节炎的疗效。方法:自2005年6月至2009年10月对62例81膝膝关节骨性关节炎患者进行关节镜下有限清理术,对其临床疗效进行分析。结果:本组病例均获随访,时间12~36个月。优28膝,良39膝,可10膝,差4膝,优良率82.7%。结论:关节镜下有限清理术治疗膝关节骨性关节炎可以有效改善病人的症状,明显改善生活质量。  相似文献   
994.
目的:考察代谢调衡饮治疗代谢综合征的临床疗效。方法:将60例代谢综合征患者随机分为试验组和对照组,对照组口服卡托普利和二甲双胍,试验组在此基础上加服代谢调衡饮,疗程3个月,观察两组治疗前后体重指数、血压、血糖、血脂等指标变化。结果:试验组有效率明显高于对照组(P<0.05)。与对照组相比,试验组患者治疗后体重指数、血压、血糖、血脂指标改善更明显(P<0.05 or P<0.01)。结论:代谢调衡饮对代谢综合征患者具有减重降压,降糖调脂功效,是干预代谢调衡饮的有效方剂。  相似文献   
995.

Background

Canine hemangiosarcoma (HSA) is a malignant tumor with poor long-term prognosis due to development of metastasis despite aggressive treatment. The phosphatidyl-inositol-3 kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is involved in its endothelial pathologies; however, it remains unknown how this pathway plays a role in canine HSA. Here, we characterized new canine HSA cell lines derived from nude mice-xenografted canine HSAs and investigated the deregulation of the signaling pathways in these cell lines.

Results

Seven canine HSA cell lines were established from 3 xenograft canine HSAs and showed characteristics of endothelial cells (ECs), that is, uptake of acetylated low-density lipoprotein and expression of canine-specific CD31 mRNA. They showed varied morphologies and mRNA expression levels for VEGF-A, bFGF, HGF, IGF-I, EGF, PDGF-B, and their receptors. Cell proliferation was stimulated by these growth factors and fetal bovine serum (FBS) in 1 cell line and by FBS alone in 3 cell lines. However, cell proliferation was not stimulated by growth factors and FBS in the remaining 3 cell lines. Phosphorylated p44/42 Erk1/2 was increased by FBS stimulation in 4 cell lines. In contrast, phosphorylation of Akt at Ser473, mTOR complex 1 (mTORC1) at Ser2448, and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) at Ser65 was high in serum-starved condition and not altered by FBS stimulation in 6 cell lines, despite increased phosphorylation of these residues in normal canine ECs. This suggested that the mTORC2/Akt/4E-BP1 pathway was constitutively activated in these 6 canine HSA cell lines. After cell inoculation into nude mice, canine HSA tumors were formed from 4 cell lines and showed Akt and 4E-BP1 phosphorylation identical to the parental cell lines.

Conclusions

Our findings suggest that the present cell lines may be useful tools for investigating the role of the mTORC2/Akt/4E-BP1 pathway in canine HSA formation both in vivo and in vitro.  相似文献   
996.
ABSTRACT: BACKGROUND: Despite the availability of evidence-based psychotherapies for depression and anxiety, they are underused in non-mental health specialty settings such as primary care. Hybrid effectiveness-implementation designs have the potential to evaluate clinical and implementation outcomes of evidence-based psychotherapies to improve their translation into routine clinical care practices. METHODS: This protocol article discusses the study methodology and implementation strategies employed in an ongoing, hybrid, type 2 randomized controlled trial with two primary aims: (1) to determine whether a brief, manualized cognitive behavioral therapy administered by Veterans Affairs Primary Care Mental Health Integration program clinicians is effective in treating depression and anxiety in a sample of medically ill (chronic cardiopulmonary diseases) primary care patients and (2) to examine the acceptability, feasibility, and preliminary outcomes of a focused implementation strategy on improving adoption and fidelity of brief cognitive behavioral therapy at two Primary Care-Mental Health Integration clinics. The study uses a hybrid type 2 effectiveness/implementation design to simultaneously test clinical effectiveness and to collect pilot data on a multifaceted implementation strategy that includes an online training program, audit and feedback of session content, and internal and external facilitation. Additionally, the study engages the participation of an advisory council consisting of stakeholders from Primary Care-Mental Health Integration, as well as regional and national mental health leaders within the Veterans Administration. It targets recruitment of 320 participants randomized to brief cognitive behavioral therapy (n = 200) or usual care (n = 120). Both effectiveness and implementation outcomes are being assessed using mixed methods, including quantitative evaluation (e.g., intent-to-treat analyses across multiple time points) and qualitative methods (e.g., focus interviews and surveys from patients and providers). Patient-effectiveness outcomes include measures of depression, anxiety, and physical health functioning using blinded independent evaluators. Implementation outcomes include patient engagement and adherence and clinician brief cognitive behavioral therapy adoption and fidelity. CONCLUSIONS: Hybrid designs are needed to advance clinical effectiveness and implementation knowledge to improve healthcare practices. The current article describes the rationale and challenges associated with the use of a hybrid design for the study of brief cognitive behavioral therapy in primary care. Although trade-offs exist between scientific control and external validity, hybrid designs are part of an emerging approach that has the potential to rapidly advance both science and practice. Trial registration NCT01149772 at http://www.clinicaltrials.gov/ct2/show/NCT01149772.  相似文献   
997.
998.
Cyclic AMP (cAMP)-dependent processes are pivotal during the early stages of adipocyte differentiation. We show that exchange protein directly activated by cAMP (Epac), which functions as a guanine nucleotide exchange factor for the Ras-like GTPases Rap1 and Rap2, was required for cAMP-dependent stimulation of adipocyte differentiation. Epac, working via Rap, acted synergistically with cAMP-dependent protein kinase (protein kinase A [PKA]) to promote adipogenesis. The major role of PKA was to down-regulate Rho and Rho-kinase activity, rather than to enhance CREB phosphorylation. Suppression of Rho-kinase impaired proadipogenic insulin/insulin-like growth factor 1 signaling, which was restored by activation of Epac. This interplay between PKA and Epac-mediated processes not only provides novel insight into the initiation and tuning of adipocyte differentiation, but also demonstrates a new mechanism of cAMP signaling whereby cAMP uses both PKA and Epac to achieve an appropriate cellular response.  相似文献   
999.
目的构建小鼠腹膜透析模型,以腹膜平衡试验(PET)曲线描述其转运特征,并观察腹膜转运关键蛋白在小鼠腹膜的表达。方法以C57BL/6小鼠为动物模型,通过PET建立透析模型,分别进行生化测定描绘PET曲线,以及蛋白印迹进行关键蛋白的检测。结果C57BL/6小鼠的PET曲线图形与人类接近。AQP-1、eNOS、Cav-1在小鼠腹膜均有稳定的表达。结论该模型结果可靠,代表性强,适合推广。  相似文献   
1000.
壳聚糖作为药物缓释控释载体的研究进展   总被引:4,自引:0,他引:4  
高娴  马世坤 《生命科学》2008,20(4):657-660
壳聚糖因其具有良好的生物学特性而成为多种药物载体研究的热点。药物经过壳聚糖负载后,不仅能够达到缓释控释的目的,还能够改变药物的给药方式,以此减少给药次数,降低药物不良反应,提高药物生物利用度。本文就壳聚糖和改性壳聚糖作为普通药物和生物大分子药物载体的研究进展作一综述。  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