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   11600篇
  免费   371篇
  11971篇
  2024年   51篇
  2023年   37篇
  2022年   140篇
  2021年   227篇
  2020年   146篇
  2019年   204篇
  2018年   320篇
  2017年   235篇
  2016年   396篇
  2015年   636篇
  2014年   749篇
  2013年   751篇
  2012年   1018篇
  2011年   937篇
  2010年   617篇
  2009年   516篇
  2008年   717篇
  2007年   600篇
  2006年   529篇
  2005年   510篇
  2004年   441篇
  2003年   381篇
  2002年   318篇
  2001年   200篇
  2000年   193篇
  1999年   140篇
  1998年   71篇
  1997年   48篇
  1996年   30篇
  1995年   49篇
  1994年   44篇
  1993年   31篇
  1992年   58篇
  1991年   52篇
  1990年   65篇
  1989年   42篇
  1988年   37篇
  1987年   33篇
  1986年   30篇
  1985年   39篇
  1984年   27篇
  1983年   28篇
  1982年   21篇
  1981年   24篇
  1979年   21篇
  1974年   18篇
  1973年   19篇
  1971年   23篇
  1970年   17篇
  1968年   19篇
排序方式: 共有10000条查询结果,搜索用时 22 毫秒
71.
In general, an antimicrobial test for screening anti-caries natural extracts was performed by measuring the minimum bactericidal concentration (MBC) against the type strains of mutans streptococci. However, it is unclear if the antimicrobial efficiency of natural extracts on the type strains of mutans streptococci is the same on the clinical strains. In this study, we introduced a bacterial model system for the screening of anti-caries and determining the optimal concentration of them to develop oral hygiene products for Korean populations.  相似文献   
72.
Japanese beetle traps baited with the Popillia japonica Newman (Coleoptera: Scarabaeidae) pheromone lure and a eugenol feeding attractant were placed at five golf courses in Korea to determine how well they work for detecting activity of a closely related species, Popillia quadriguttata (F.) (Coleoptera: Scarabaeidae), a turf pest in Korea. The traps also were used to determine the time of day and time of year that P. quadriguttata is most active. Nineteen scarab species of 13 genera were attracted to the Japanese beetle traps with P. quadriguttata clearly being the most abundant (383 beetles per trap), followed by Adoretus tenuimaculatus Waterhouse (10 per trap), Popilliaflavosellata Fairmaire (seven per trap), Exomala orientalis Waterhouse (four per trap), and Maladera japonica (two per trap). Other scarab species were trapped at a rate of <1.0 per trap. Popillia quadriguttata adults were active over a 5-wk period in late June and early July. At Yongwon Golf Club in 2002, peak adult activity was during the last week of June in visual counts and approximately 1 wk later in the Japanese beetle traps. In Korea, P. quadriguttata adults are most active between 12:00 p.m. and 4:00 p.m. This information should be helpful to golf course superintendents in Korea and to entomologists interested in finding natural enemies of P. quadriguttata to evaluate as potential biocontrol organisms for the very closely related species, the Japanese beetle.  相似文献   
73.
    
The Spo0B-associated GTP-binding protein (Obg) GTPase, essential for bacterial viability, is also conserved in eukaryotes, but its primary role in eukaryotes remains unknown. Here, our functional characterization of Arabidopsis and rice obgc mutants strongly underlines the evolutionarily conserved role of eukaryotic Obgs in organellar ribosome biogenesis. The mutants exhibited a chlorotic phenotype, caused by retarded chloroplast development. A plastid DNA macroarray revealed a plastid-encoded RNA polymerase (PEP) deficiency in an obgc mutant, caused by incompleteness of the PEP complex, as its western blot exhibited reduced levels of RpoA protein, a component of PEP. Plastid rRNA profiling indicated that plastid rRNA processing is defective in obgc mutants, probably resulting in impaired ribosome biogenesis and, in turn, in reduced levels of RpoA protein. RNA co-immunoprecipitation revealed that ObgC specifically co-precipitates with 23S rRNA in vivo. These findings indicate that ObgC functions primarily in plastid ribosome biogenesis during chloroplast development. Furthermore, complementation analysis can provide new insights into the functional modes of three ObgC domains, including the Obg fold, G domain and OCT.  相似文献   
74.
  总被引:3,自引:6,他引:3  
The pediocin-like bacteriocins, produced by lactic acid bacteria, are bactericidal polypeptides with very similar primary structures. Peptide synthesis followed by reverse-phase and ion-exchange chromatographies yielded biologically active pediocin-like bacteriocins in amounts and with a purity sufficient for characterizing their structure and mode of action. Despite similar primary structures, the pediocin-like bacteriocins, i.e., pediocin PA-1, sakacin P, curvacin A, and leucocin A, differed in their relative toxicities against various bacterial strains. On the basis of the primary structures, the polypeptides of these bacteriocins were divided into two modules: the relatively hydrophilic and well conserved N-terminal region, and the somewhat more diverse and hydrophobic C-terminal region. By peptide synthesis, four new biologically active hybrid bacteriocins were constructed by interchanging corresponding modules from various pediocin-like bacteriocins. All of the new hybrid bacteriocin constructs had bactericidal activity. The relative sensitivity of different bacterial strains to a hybrid bacteriocin was similar to that to the bacteriocin from which the C-terminal module was derived and quite different from that to the bacteriocin from which the N-terminal was derived. Thus, the C-terminal part of the pediocin-like bacteriocins is an important determinant of the target cell specificity. The synthetic bacteriocins were more stable than natural isolates, presumably as a result of the absence of contaminating proteases. However, some of the synthetic bacteriocins lost activity, but this was detectable only after months of storage. Mass spectrometry suggested that this instability was due to oxidation of methionine residues, resulting in a 10- to 100-fold reduction in activity.  相似文献   
75.
76.
Acute liver failure, the fatal deterioration of liver function, is the most common indication for emergency liver transplantation, and drug-induced liver injury and viral hepatitis are frequent in young adults. Stem cell therapy has come into the limelight as a potential therapeutic approach for various diseases, including liver failure and cirrhosis. In this study, we investigated therapeutic effects of tonsil-derived mesenchymal stem cells (T-MSCs) in concanavalin A (ConA)- and acetaminophen-induced acute liver injury. ConA-induced hepatitis resembles viral and immune-mediated hepatic injury, and acetaminophen overdose is the most frequent cause of acute liver failure in the United States and Europe. Intravenous administration of T-MSCs significantly reduced ConA-induced hepatic toxicity, but not acetaminophen-induced liver injury, affirming the immunoregulatory capacity of T-MSCs. T-MSCs were successfully recruited to damaged liver and suppressed inflammatory cytokine secretion. T-MSCs expressed high levels of galectin-1 and -3, and galectin-1 knockdown which partially diminished interleukin-2 and tumor necrosis factor α secretion from cultured T-cells. Galectin-1 knockdown in T-MSCs also reversed the protective effect of T-MSCs on ConA-induced hepatitis. These results suggest that galectin-1 plays an important role in immunoregulation of T-MSCs, which contributes to their protective effect in immune-mediated hepatitis. Further, suppression of T-cell activation by frozen and thawed T-MSCs implies great potential of T-MSC banking for clinical utilization in immune-mediated disease.  相似文献   
77.
Modification of proteins by the covalent attachment of ubiquitin is a key regulatory mechanism of many cellular processes including protein degradation by the 26S proteasome. Deubiquitination, reversal of this modification, must also regulate the fate and function of ubiquitin-conjugated proteins. Deubiquitinating enzymes catalyze the removal of ubiquitin from ubiquitin-conjugated substrate proteins as well as from its precursor proteins. Deubiquitinating enzymes occupy the largest family of enzymes in the ubiquitin system, implying their diverse function in regulation of the ubiquitin-mediated pathways. Here we explore the diversity of deubiquitinating enzymes and their emerging roles as cellular regulators.  相似文献   
78.
79.
  总被引:3,自引:0,他引:3  
BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces cell death in various tumor cells, but relatively spares normal cells. Recombinant adeno-associated virus (rAAV) vectors have a number of advantages including in vivo long-term gene expression. Here, we assessed the biological activity of a novel, secreted form of TRAIL (sTRAIL) for cancer gene therapy using a rAAV2 vector. METHODS: A plasmid and rAAV2 vectors were constructed encoding sTRAIL composed of a leader sequence, the isoleucine zipper, and the active domain of TRAIL (aa 95-281). The functionality of sTRAIL was validated by cell viability, FACS analysis, caspase-3 activity, and TUNEL staining. rAAV-sTRAIL was injected intratumorally to nude mice bearing human A549 lung tumor cells. Nude mice received A549 tumor cells after intravenous delivery of rAAV-sTRAIL. The antitumor effect was then evaluated by measuring tumor regression and occurrence in the experimental animal. RESULTS: sTRAIL was released from cells transfected with the sTRAIL expression construct or transduced with rAAV-sTRAIL, and induced apoptosis in cancer cells, but spared normal fibroblast cells. Secreted sTRAIL formed oligomers including trimers with intersubunit disulfide. Purified sTRAIL exerted much lower cytotoxicity on primary human hepatocytes compared to recombinant TRAIL. Intratumoral delivery of rAAV-sTRAIL significantly inhibited growth of A549 tumors established in nude mice. A number of apoptotic tumor cells were detected by TUNEL staining in mice treated with rAAV-sTRAIL. Systemic pretreatment with rAAV-sTRAIL significantly inhibited tumor formation in nude mice. CONCLUSION: The results suggest that rAAV-sTRAIL may be useful for local or systemic cancer gene therapy for treating TRAIL-sensitive tumors.  相似文献   
80.
ABP(57) is an auxin-binding protein that possesses receptor function. In this study, a protocol for ABP(57) purification was developed on the basis of cross-reactivity shown between ABP(57) and antisera raised against bovine serum albumin, which enabled us to purify ABP(57) with a high yield and to further characterize it. ABP(57) activates plant plasma membrane H(+)-ATPase (PM H(+)-ATPase) via direct interaction. The binding of indole-3-acetic acid (IAA) to the primary binding site on ABP(57) caused a marked increase in the affinity of ABP(57) for PM H(+)-ATPase, which was accompanied by a change in ABP(57) conformation. Meanwhile, additional IAA binding to the secondary site on ABP(57) nullified the initial effect without inducing further conformational change. When ABP(57) with IAA occupying only the primary site interacted with PM H(+)-ATPase, no IAA could access the secondary site. These results suggest that IAA-induced biphasic alteration in the affinity of ABP(57) for PM H(+)-ATPase correlates with a bell-shaped dose response of the enzyme to IAA. There is also a possibility that, whereas the stimulation phase of the response is associated with a conformational change of ABP(57), the destimulation phase probably results from hindrance arising directly from the presence of IAA at the secondary site.  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