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   3823篇
  免费   379篇
  国内免费   273篇
  4475篇
  2024年   8篇
  2023年   33篇
  2022年   69篇
  2021年   148篇
  2020年   100篇
  2019年   148篇
  2018年   144篇
  2017年   120篇
  2016年   164篇
  2015年   262篇
  2014年   275篇
  2013年   293篇
  2012年   367篇
  2011年   323篇
  2010年   209篇
  2009年   190篇
  2008年   230篇
  2007年   201篇
  2006年   163篇
  2005年   140篇
  2004年   138篇
  2003年   127篇
  2002年   118篇
  2001年   66篇
  2000年   52篇
  1999年   53篇
  1998年   26篇
  1997年   20篇
  1996年   24篇
  1995年   16篇
  1994年   20篇
  1993年   20篇
  1992年   22篇
  1991年   14篇
  1990年   17篇
  1989年   9篇
  1988年   13篇
  1987年   10篇
  1986年   16篇
  1985年   6篇
  1984年   12篇
  1983年   11篇
  1982年   5篇
  1981年   5篇
  1980年   7篇
  1979年   4篇
  1978年   6篇
  1976年   8篇
  1975年   10篇
  1974年   9篇
排序方式: 共有4475条查询结果,搜索用时 0 毫秒
991.
Simvastatin has been shown to promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Our study aimed to illuminate the underlying mechanism, with a specific focus on the role of Hedgehog signaling in this process. BMSCs cultured with or without 10−7 mol/L simvastatin were subjected to evaluation of osteogenic differentiation capacity. Osteogenic markers such as type 1 collagen (COL1) and osteocalcin (OCN), as well as key molecules of Hedgehog signaling molecules, were examined by Western blot and real-time polymerase chain reaction (PCR). Co-immunoprecipitation and mass spectrometry assays were applied to screen for Gli1-interacting proteins. Cyclopamine (Cpn) was used as a Hedgehog signaling inhibitor. Our results indicated that simvastatin increased alkaline phosphatase (ALP) activity; mineralization of extracellular matrix; mRNA expression of ALP, COL1, and OCN; and expression and nuclear translocation of Gli1. Contrasting effects were observed in Cpn-exposed groups, but were partially rescued by the simvastatin treatment. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that Gli1-interacting proteins were primarily associated with mitogen-activated protein kinase (MAPK) (P = 7.04E−04), hippo, insulin, and glucagon signaling. Further, hub genes identified by protein-protein interaction network analysis included Gli1-interacting proteins such as Ppp2r1a, Rac1, Etf1, and XPO1/CRM1. In summary, the current study showed that the mechanism by which simvastatin stimulates osteogenic differentiation of BMSCs involves activation of Hedgehog signaling, as indicated by interactions with Gli1 and, most notably, the MAPK signaling pathway.  相似文献   
992.
Syntheses and radical scavenging activities of resveratrol derivatives   总被引:3,自引:0,他引:3  
Nine new resveratrol derivatives, having bromo, iodo, and fluoroethyl groups, were designed and synthesized. All compounds having free phenol groups showed good free radical scavenging activity. Among them, 2-bromoresveratrol 19 has a similar free radical scavenging activity to (+)-catechin.  相似文献   
993.
畜禽粪便堆肥过程中氮素的损失与控制   总被引:37,自引:0,他引:37  
堆肥是实现畜禽粪便处理及资源化利用的有效途径,然而畜禽粪便堆肥过程中氮素损失较严重,对氮素损失与控制的研究可为有效控制氮素损失提供理论基础和实践参考.本文简述了畜禽粪便堆肥过程中氮素转化及主要损失途径,总结了影响堆肥氮素损失的主要因素(包括堆肥物料初始特性、堆肥环境参数和堆肥工艺条件),并综述了氮素损失控制措施(调节C、N代谢,改变氮素形态,添加NH3吸附剂和调节通风与控温措施)的研究进展,此外,对未来的研究方向进行了展望.  相似文献   
994.
对虾病毒病病毒和细菌合并感染的病理特点和诊断价值   总被引:1,自引:0,他引:1  
应用电镜超薄切片及光学石蜡切片和环氧树脂薄片技术,观察健康对照组、疾病始发组和濒临死亡组的草虾、中国对虾、日本对虾和长毛对虾的肝胰腺和中肠,结果在3组4种对虾中均检测到病毒,只在濒临死亡组的4种对虾中发现病毒与细菌的合并感染。合并感染的病毒有MBV、球形病毒和淋巴样细胞核型杆状病毒。细菌以弧菌为主,其病理变化表现为器官和组织的保护层受损、溶解样坏死和凝固样坏死。仅以病毒和细菌合并感染作为养殖对虾病毒病早期诊断的指标是不够的,仅可作为辅助性诊断指标。但合并感染对评估对虾病毒病的预后以指导捕捞,却有一定意义。  相似文献   
995.
外源有机物的输入可以通过正负激发效应影响土壤有机碳(SOC)的矿化。然而, 当前的研究较少考虑不同植物及器官来源可溶性有机质(DOM)输入对土壤激发效应的影响及其作用机理。该研究以武夷山森林土壤为研究对象, 以室内培养的方式向土壤中添加13C标记青冈(Cyclobalanopsis glauca)、杉木(Cunninghamia lanceolata)、木莲(Manglietia fordiana)和相思(Acacia confusa)这4种植物的根和叶来源DOM, 研究不同植物及器官来源DOM输入对土壤激发效应的影响及其作用机理。主要结果: 不同植物及器官来源DOM添加初期加快了SOC的矿化, 呈现正激发效应, 随后转为负激发效应。从整个培养期(90天)的累积激发效应来看, DOM的输入均抑制了SOC的矿化, 使其矿化量减少22%-49%, 其中青冈根DOM输入使SOC的矿化量减少最多, 而由木莲叶DOM输入减少的SOC矿化量最少。DOM输入引起的土壤激发效应强度受不同植物器官影响明显, 具体表现在植物根来源DOM输入所引起的土壤激发效应强度显著高于植物叶来源DOM输入所引起的激发效应强度(相思除外)。DOM的输入总体上提高了土壤微生物生物量碳(MBC)含量、土壤β-葡萄糖苷酶活性、纤维素酶活性以及土壤有效氮含量, 而对微生物群落组成无明显影响。从结构方程模型来看, DOM输入所引起的土壤激发效应主要受土壤微生物对外源碳的利用(13C-MBC)、纤维素酶活性以及土壤有效氮含量的影响, 这些因子的变化可解释植物叶来源DOM和根来源DOM添加处理下土壤激发效应变化的68%和86%。该研究结果表明在土壤氮充足的条件下, DOM的输入可以通过提高微生物生物量、土壤酶活性来加快分解所添加的外源有机物, 从而减少了对SOC的分解。因此, 在该研究中“底物优先利用”是土壤激发效应的主要作用机理。  相似文献   
996.
Gynostemma pentaphyllum saponins (GpS) have been shown to have anti‐cancer activity. However, the underlying mechanisms remain unclear. In this study, we used the ApcMin/+ colorectal cancer (CRC) mouse model to investigate the anti‐cancer effect of GpS and we demonstrated that GpS treatment could significantly reduce the number and size of intestinal polyps in ApcMin/+ mice. In order to identify the potential targets and mechanisms involved, a comparative proteomics analysis was performed and 40 differentially expressed proteins after GpS treatment were identified. Bioinformatics analyses suggested a majority of these proteins were involved in processes related to cellular redox homeostasis, and predicted Raf‐1 as a potential target of GpS. The upregulation of two proteins known to be involved in redox homeostasis, peroxiredoxin‐1 (Prdx1) and peroxiredoxin‐2 (Prdx2), and the downregulation of Raf‐1 were validated using Western blot analysis. After further investigation of the associated signaling networks, we postulated that the anti‐cancer effect of GpS was mediated through the upregulation of Prdx1 and Prdx2, suppression of Ras, RAF/MEK/ERK/STAT, PI3K/AKT/mTOR signaling and modulation of JNK/p38 MAPK signaling. We also examined the potential combinatorial effect of GpS with the chemotherapeutic 5‐fluorouracil (5‐FU) and found that GpS could enhance the anti‐cancer efficacy of 5‐FU, further suppressing the number of polyps in ApcMin/+ mice. Our findings highlight the potential of GpS as an anti‐cancer agent, the potential mechanisms of its anti‐cancer activities, and its effect as an adjuvant of 5‐FU in the chemotherapy of CRC.  相似文献   
997.
中国特有种四合木种群遗传多样性的RAPD分析   总被引:7,自引:6,他引:7  
张颖娟  杨持 《生态学报》2002,22(11):1917-1922
采用随机扩增多态性 DNA(RAPD)技术检测了西鄂尔多斯高原特有种四合木种群 5个斑块的遗传多样性。2 2个扩增引物产生 1 1 6条带 ,Shannon信息指数和 Nei指数对 RAPD数据的分析表明 :四合木种群存在较高的遗传多样性 ,其中千里山斑块的遗传多样性和多态位点比例较高 ,石嘴山斑块的最低。遗传多样性的 86.5 %存在于斑块内 ,斑块间的遗传变异为 1 3 .5 %。遗传距离与地理距离无直接相关关系。这些结果说明 ,遗传多样性反映了四合木种群基因组 DNA存在较高的变异性 ;同时各斑块间存在一定的基因流 ,四合木各斑块可看成是处于同一种群的半隔离状态 (meta-种群 ) ,对四合木应注意保护遗传多样性丰富的 meta-种群。  相似文献   
998.
BackgroundMicroRNA-21 (miRNA-21 or miR-21) may act as a prognostic biomarker of cancer. However, the available evidence is controversial. Therefore, the present meta-analysis summarizes this evidence and evaluates the prognostic role of this gene in breast cancer.MethodsThe meta-analysis was conducted by searching the databases of PubMed, EMBASE, Web of Science and Chinese database-China National Knowledge Infrastructure (CNKI). Data were extracted from studies that investigated the association between miR-21 expression and survival outcomes in breast cancer patients. With respect to survival outcomes, the pooled hazard ratios (HRs) of miR-21 were calculated given a 95% confidence interval (CI).ResultsOur meta-analysis identified a total of 10 studies involving 1,439 cases. Further investigation demonstrated that a high miR-21 expression can predict poor overall survival (OS) (HR = 2.57, 95% CI: 1.37—4.81, P = 0.003) and shortened disease-free/recurrence-free survival (DFS/RFS) (HR = 1.45, 95% CI: 1.16—1.82, P = 0.001) in breast cancer patients. Moreover, high miR-21 expression was significantly correlated with lowered OS in the Asian group (HR = 5.07, 95% CI: 2.89—8.92, P < 0.001), but not in the Caucasian cohort (HR = 1.44, 95% CI: 0.99—2.10, P = 0.058). Furthermore, odds ratios (ORs) showed that up-regulated miR-21 levels were associated with multiple clinical characteristics.ConclusionOur results indicated that miR-21 can predict unfavorable prognoses in breast cancer patients, especially in Asians.  相似文献   
999.
目的寻找一种较好的成年大鼠气管插管方法;方法对比明视经口气管内插管法与逆行导管引导插管法的成功率及并发症;结果明视经口气管内插管法的成功率为100%,逆行导管引导插管法的成功率为87%。插管后并发症明显低于逆行导管引导插管法。结论明视经口气管内插管法优于逆行导管引导插管法,值得推广应用。  相似文献   
1000.
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