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   2063篇
  免费   84篇
  国内免费   60篇
  2023年   28篇
  2022年   15篇
  2021年   22篇
  2020年   35篇
  2019年   50篇
  2018年   67篇
  2017年   42篇
  2016年   33篇
  2015年   44篇
  2014年   98篇
  2013年   172篇
  2012年   80篇
  2011年   110篇
  2010年   76篇
  2009年   73篇
  2008年   93篇
  2007年   87篇
  2006年   83篇
  2005年   70篇
  2004年   49篇
  2003年   57篇
  2002年   47篇
  2001年   32篇
  2000年   27篇
  1999年   26篇
  1998年   27篇
  1997年   24篇
  1996年   17篇
  1995年   15篇
  1994年   15篇
  1993年   14篇
  1992年   11篇
  1991年   10篇
  1990年   12篇
  1988年   8篇
  1987年   7篇
  1985年   36篇
  1984年   50篇
  1983年   25篇
  1982年   39篇
  1981年   59篇
  1980年   39篇
  1979年   41篇
  1978年   37篇
  1977年   38篇
  1976年   33篇
  1975年   40篇
  1974年   38篇
  1973年   36篇
  1971年   6篇
排序方式: 共有2207条查询结果,搜索用时 15 毫秒
961.
962.
The diversity of natural compounds is essential for their mechanism of action. The source, structures and structure activity relationship of natural compounds contributed to the development of new classes of chemotherapy agents for over 40?years. The availability of combinatorial chemistry and high-throughput screening has fueled the challenge to identify novel compounds that mimic nature's chemistry and to predict their macromolecular targets. Combining conventional and targeted therapies helped to successfully overcome drug resistance and prolong disease-free survival. Here, we aim to provide an overview of preclinical investigated natural compounds alone and in combination to further improve personalization of cancer treatment.  相似文献   
963.
The quinazolinone-containing 2,3-disubstituted piperidines febrifugine and isofebrifugine have been the subject of significant research efforts since their occurrence in Dichroa febrifuga and their anti-malarial actions were first described in the late 1940s. Subsequently they have also been shown to be present in other plants belonging to the hydrangea family and various analogues of febrifugine have been prepared in attempts to tune biological properties. The most notable analogue is termed halofuginone and a substantial body of work now demonstrates that this compound possesses potent human disease relevant activities. This review focuses on the literature associated with efforts dedicated towards uncovering the structures of febrifugine and isofebrifugine, the development of practical methods for their synthesis and the syntheses of structural analogues.  相似文献   
964.
该研究以雷公藤发状根为材料,根据雷公藤根转录组数据设计引物,采用RT-PCR方法克隆得到2个雷公藤AP2/ERF转录因子,分别命名为TwAP2/ERF1基因(GenBank登录号:GAVZ01042389.1)和TwAP2/ERF2基因(GenBank登录号:GAVZ01016765.1)。TwAP2/ERF1基因含有一个525bp开放阅读框(ORF),编码186个氨基酸;TwAP2/ERF2基因的ORF为789bp,编码262个氨基酸;2个基因编码的蛋白质均为亲水性蛋白质。系统进化分析表明,TwAP2/ERF1与油桐(Vernicia fordii)AP2/ERF(APQ47444.1)和木油桐(Vernicia montana)AP2/ERF(APQ47365.1)相似性较高,TwAP2/ERF2与毛果杨(Populus trichocarpa)AP2/ERF(XP_002304640.1)和樱桃(Prunus pseudocerasus)AP2/ERF(ALD84477.1)相似性较高。雷公藤发状根经MeJA诱导后,TwAP2/ERF1基因的相对表达量明显提高,并于处理后9h达到最高值,为对照表达量的16.77倍;而MeJA处理对TwAP2/ERF2基因的表达表现出抑制作用,但于处理后48h相对表达量有所提高。研究表明,雷公藤TwAP2/ERF1转录因子响应MeJA早期诱导正调控,推测其可能参与调控雷公藤植物次生代谢产物的生物合成,该研究结果为阐明雷公藤次生代谢物质的生物合成调控与利用现代生物技术提高雷公藤植物细胞中次生代谢物质的含量奠定了基础。  相似文献   
965.
The selective autophagic removal of mitochondria called mitophagy is an essential physiological signaling for clearing damaged mitochondria and thus maintains the functional integrity of mitochondria and cells. Defective mitophagy is implicated in several diseases, placing mitophagy as a target for drug development. The identification of key regulators of mitophagy as well as chemical modulators of mitophagy requires sensitive and reliable quantitative approaches. Since mitophagy is a rapidly progressing event and sub-microscopic in nature, live cell image-based detection tools with high spatial and temporal resolution is preferred over end-stage assays. We describe two approaches for measuring mitophagy in mammalian cells using stable cells expressing EGFP-LC3 – Mito-DsRed to mark early phase of mitophagy and Mitochondria-EGFP – LAMP1-RFP stable cells for late events of mitophagy. Both the assays showed good spatial and temporal resolution in wide-field, confocal and super-resolution microscopy with high-throughput adaptable capability. A limited compound screening allowed us to identify a few new mitophagy inducers. Compared to the current mitophagy tools, mito-Keima or mito-QC, the assay described here determines the direct delivery of mitochondrial components to the lysosome in real time mode with accurate quantification if monoclonal cells expressing a homogenous level of both probes are established. Since the assay described here employs real-time imaging approach in a high-throughput mode, the platform can be used both for siRNA screening or compound screening to identify key regulators of mitophagy at decisive stages.  相似文献   
966.
Ghrelin is a small peptide hormone that undergoes a unique posttranslational modification, serine octanoylation, to play its physiological roles in processes including hunger signaling and glucose metabolism. Ghrelin O-acyltransferase (GOAT) catalyzes this posttranslational modification, which is essential for ghrelin to bind and activate its cognate GHS-R1a receptor. Inhibition of GOAT offers a potential avenue for modulating ghrelin signaling for therapeutic effect. Defining the molecular characteristics of ghrelin that lead to binding and recognition by GOAT will facilitate the development and optimization of GOAT inhibitors. We show that small peptide mimics of ghrelin substituted with 2,3-diaminopropanoic acid in place of the serine at the site of octanoylation act as submicromolar inhibitors of GOAT. Using these chemically modified analogs of desacyl ghrelin, we define key functional groups within the N-terminal sequence of ghrelin essential for binding to GOAT and determine GOAT’s tolerance to backbone methylations and altered amino acid stereochemistry within ghrelin. Our study provides a structure-activity analysis of ghrelin binding to GOAT that expands upon activity-based investigations of ghrelin recognition and establishes a new class of potent substrate-mimetic GOAT inhibitors for further investigation and therapeutic interventions targeting ghrelin signaling.  相似文献   
967.
A study was conducted to characterize changes in bermudagrass (Cynodon dactylon [L.] Pers.) and tall fescue (Festuca arundinacea Schreb.) root development over time and with depth, and to determine the effects of defoliation interval and chemical seedhead suppression on root and shoot growth. Field plots were established on a fine-silty, mixed mesic Typic Fragiudult soil in Fayetteville, AR, USA, and each plot contained three minirhizotrons (plexiglass observation tubes) to a depth of 40 cm. Images of roots in 10-cm depth increments were periodically videorecorded, and total root length (RL) and root length density (RLD) were measured with a computer-interfaced tracing probe. Treatments consisted of two cutting intervals, 3 and 6 weeks, and two plant growth regulator (PGR) treatments, an untreated control and either 300 g ha-1 mefluidide on tall fescue in early spring of both years or 10 g ha-1 each of metsulfuron methyl (MSM) and sulfometuron methyl (SMM) applied in late May of both post-establishment years. Data were analyzed separately for the establishment period (planting to the first date of PGR application) and the subsequent post-establishment period. Bermulagrass exhibited a two-stage root establishment pattern characterized first by minimal root development in conjunction with stolon proliferation and soil surface colonization, followed by accumulation of total RL over two subsequent forage production seasons. There was a net accumulation of root mass during the winter dormancy period of 1986–87. Total RL of tall fescue peaked one and a half years after planting. Cutting interval had no influence on RL and RLD. Application of a PGR did not affect RL but did alter RLD of both species. Application of mefluidide to tall fescue stimulated RLD 64 days after application, whereas bermudagrass RLD was retarded by MSM and SMM up to 50 days after application. Trends in root growth did not closely follow patterns of shoot growth. Published with the approval of the Director of the Arkansas Agricultural Experiment Station. Published with the approval of the Director of the Arkansas Agricultural Experiment Station.  相似文献   
968.
Aqueous extracts from 33 species of marine algae were assessed for their methyl mercaptan-trapping activity by gas chromatography to search for novel natural oral deodorants. Brown algae belonging to the Laminariales such as Eisenia bicyclis, Ecklonia cava and Ecklonia kurome were found to show remarkable deodorizing action against methyl mercaptan. The effective components in Eisenia bicyclis were identified as a phlorotannin, a group of molecules which are characteristic components of Laminariales. In addition phlorotannins extracted from E. bicyclis were more effective at reducing methyl mercaptan than conventional natural deodorants such as chlorophyll and sodium copper chlorophyllin.Author for Correspondence  相似文献   
969.
The deacetyiation of methyl 2,3,4-tri-O-acetyl-β-D-ylopyranoside was studied under different conditions of alkaline and enzymic hydrolysis. During enzymic deacetylation using porcine liver esterase a considerably higher amount of partially acetylated derivatives was observed in contrast to chemical hydrolysis.  相似文献   
970.
Summary A preparative-scale enantioselective hydrolysis of racemic methyl esters of several N-protected amino acid has been carried out by using crude porcine pancreatic lipase (Triacylglycerol lipase, EC 3.1.1.3) PPL as a hydrolytic enzyme. In all cases 50% of the racemic methyl ester was hydrolysed to the N-protected L-amino acid with high yield and high optical purity.Hydrolysis rates were very close related not only to the amino acid structure but also to the steric and/or electronic nature of the ester and N-protecting groups. Thus, the very convenient ester methyl group can be enantioselectively hydrolysed with PPL when N-protecting group is a carbonyl derivative, as it is the usual benzoyl group.  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