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   1736篇
  免费   125篇
  2022年   7篇
  2021年   16篇
  2020年   14篇
  2019年   13篇
  2018年   16篇
  2017年   17篇
  2016年   41篇
  2015年   61篇
  2014年   88篇
  2013年   106篇
  2012年   148篇
  2011年   192篇
  2010年   131篇
  2009年   97篇
  2008年   104篇
  2007年   84篇
  2006年   75篇
  2005年   67篇
  2004年   86篇
  2003年   79篇
  2002年   74篇
  2001年   10篇
  2000年   11篇
  1999年   16篇
  1998年   32篇
  1997年   12篇
  1996年   19篇
  1995年   16篇
  1994年   16篇
  1993年   12篇
  1992年   12篇
  1991年   18篇
  1990年   16篇
  1989年   9篇
  1988年   16篇
  1987年   9篇
  1986年   4篇
  1985年   13篇
  1984年   15篇
  1983年   9篇
  1982年   9篇
  1981年   8篇
  1980年   6篇
  1979年   5篇
  1978年   6篇
  1977年   4篇
  1976年   6篇
  1974年   5篇
  1973年   4篇
  1972年   5篇
排序方式: 共有1861条查询结果,搜索用时 46 毫秒
101.
A new biomimetic route for the synthesis of a conducting molecular complex of polyaniline (Pani) and a natural polyelectrolyte, lignosulfonate (LGS) is presented. A poly(ethylene glycol) modified hematin (PEG-hematin) was used to catalyze the polymerization of aniline in the presence of LGS to form a Pani/LGS complex. UV-vis, FTIR, conductivity and TGA studies for the LGS-polyaniline complex indicate the presence of a thermally stable and electrically conductive form of polyaniline. Also the presence of LGS in this complex, an inexpensive byproduct from pulp processing, provides a unique combination of properties such as electronic conductivity, processability and biodegradability. The use of this conductive complex for corrosion protection is also proposed.  相似文献   
102.
In the Ceramiaceae, one of the largest families of the red algae, there are from 1 to 4000 nuclei in each vegetative cell, but each tribe is homogeneous with respect to the uninucleate/multinucleate character state, except for the Callithamnieae. The goals of this study were to analyze rbcL gene sequences to clarify the evolution of taxa within the tribe Callithamnieae and to evaluate the potential evolutionary significance of the development of multinucleate cells in certain taxa. The genus Aglaothamnion, segregated from Callithamnion because it is uninucleate, was paraphyletic in all analyses. Callithamnion (including Aristothamnion) was monophyletic although not robustly so, apparently due to variations between taxa in rate of sequence evolution. Morphological synapomorphies were identified at different depths in the tree, supporting the molecular phylogenetic analysis. The uninucleate character state is ancestral in this tribe. The evolution of multinucleate cells has occurred once in the Callithamnieae. Multiple nuclei in each cell may combine the benefits of small C values (rapid cell cycle) with large cells (permitting morphological elaboration) while maintaining a constant ratio of nuclear volume: cytoplasmic volume.  相似文献   
103.
Nonsense-mediated mRNA decay (NMD) in mammalian cells depends on phosphorylation of Upf1, an RNA-dependent ATPase and 5'-to-3' helicase. Upf1 phosphorylation is mediated by Smg1, a phosphoinositol 3-kinase-related protein kinase. Here, we describe a human protein, which we call hSmg5/7a, that manifests similarity to Caenorhabditis elegans NMD factors CeSMG5 and CeSMG7, as well as two Drosophila melanogaster proteins that are also similar to the C. elegans NMD factors. Results indicate that hSmg5/7a functions in the dephosphorylation of Upf1. Furthermore, hSmg5/7a copurifies with Upf1, Upf2, Upf3X, Smg1, and the catalytic subunit of protein phosphatase 2A. We also demonstrate that Upf2, another factor involved in NMD, is a phosphoprotein. However, hSmg5/7a plays no role in the dephosphorylation of Upf2. These data indicate that hSmg5/7a targets protein phosphatase 2A to Upf1 but not Upf2. Results of Western blotting reveal that hSmg5/7a is mostly cytoplasmic in HEK293T cells.  相似文献   
104.
Catecholamines stimulate cardiac contractility through beta(1)-adrenergic receptors (beta(1)-ARs), which in humans are polymorphic at amino acid residue 389 (Arg/Gly). We used cardiac-targeted transgenesis in a mouse model to delineate mechanisms accounting for the association of Arg389 with human heart failure phenotypes. Hearts from young Arg389 mice had enhanced receptor function and contractility compared with Gly389 hearts. Older Arg389 mice displayed a phenotypic switch, with decreased beta-agonist signaling to adenylyl cyclase and decreased cardiac contractility compared with Gly 389 hearts. Arg389 hearts had abnormal expression of fetal and hypertrophy genes and calcium-cycling proteins, decreased adenylyl cyclase and G alpha(s) expression, and fibrosis with heart failure This phenotype was recapitulated in homozygous, end-stage, failing human hearts. In addition, hemodynamic responses to beta-receptor blockade were greater in Arg389 mice, and homozygosity for Arg389 was associated with improvement in ventricular function during carvedilol treatment in heart failure patients. Thus the human Arg389 variant predisposes to heart failure by instigating hyperactive signaling programs leading to depressed receptor coupling and ventricular dysfunction, and influences the therapeutic response to beta-receptor blockade.  相似文献   
105.

Background

Cilia and flagella are often lost in anticipation of mitosis or in response to stress. There are two ways that a cell can lose its flagella: resorption or deflagellation. Deflagellation involves active severing of the axoneme at the base of the flagellum; this process is defective in Chlamydomonas fa mutants. In contrast, resorption has been thought to occur as a consequence of constitutive disassembly at the tip in the absence of continued assembly, which requires intraflagellar transport (IFT). Chlamydomonas fla mutants are unable to build and maintain flagella due to defects in IFT.

Results

fla10 cells, which are defective in kinesin-II, the anterograde IFT motor, resorb their flagella at the restrictive temperature (33°C), as previously reported. We find that in standard media containing ~300 microM calcium, fla10 cells lose flagella by deflagellation at 33°C. This temperature-induced deflagellation of a fla mutant is not predicted by the IFT-based model for flagellar length control. Other fla mutants behave similarly, losing their flagella by deflagellation instead of resorption, if adequate calcium is available. These data suggest a new model whereby flagellar resorption involves active disassembly at the base of the flagellum via a mechanism with components in common with the severing machinery of deflagellation. As predicted by this model, we discovered that deflagellation stimuli induce resorption if deflagellation is blocked either by mutation in a FA gene or by lack of calcium. Further support for this model comes from our discovery that fla10-fa double mutants resorb their flagella more slowly than fla10 mutants.

Conclusions

Deflagellation of the fla10 mutant at the restrictive temperature is indicative of an active disassembly signal, which can manifest as either resorption or deflagellation. We propose that when IFT is halted by either an inactivating mutation or a cellular signal, active flagellar disassembly is initiated. This active disassembly is distinct from the constitutive disassembly which plays a role in flagellar length control.
  相似文献   
106.
Bile acids are cytoprotective in hepatocytes by activating phosphatidylinositol-3-kinase (PI3-K) and its downstream signal AKT. Our aim was to determine whether feeding taurocholate to CCl(4)-treated rats reduces cholangiocyte apoptosis and whether this cytoprotective effect is dependent on PI3-K. Cholangiocyte proliferation, secretion, and apoptosis were determined in cholangiocytes from bile duct ligation (BDL), CCl(4)-treated BDL rats, and CCl(4)-treated taurocholate-fed rats. In vitro, we tested whether CCl(4) induces apoptosis and whether loss of cholangiocyte proliferation and secretion is dependent on PI3-K. The CCl(4)-induced cholangiocyte apoptosis and loss of cholangiocyte proliferation and secretion were reduced in CCl(4)-treated rats fed taurocholate. CCl(4)-induced cholangiocyte apoptosis, loss of cholangiocytes secretion, and proliferation were prevented by preincubation with taurocholate. Taurocholate cytoprotective effects were ablated by wortmannin. Taurocholate prevented, in vitro, CCl(4)-induced decrease of phosphorylated AKT protein expression in cholangiocytes. The cytoprotective effects of taurocholate on CCl(4) effects on cholangiocyte proliferation and secretion were abolished by wortmannin. Taurocholate protects cholangiocytes from CCl(4)-induced apoptosis by a PI3-K-dependent mechanism. Bile acids are important in the prevention of drug-induced ductopenia in cholangiopathies.  相似文献   
107.
Structure and function of S-adenosylhomocysteine hydrolase   总被引:6,自引:0,他引:6  
In mammals, S-adenosylhomocysteine hydrolase (AdoHcyase) is the only known enzyme to catalyze the breakdown of S-adenosylhomocysteine (AdoHcy) to homocysteine and adenosine. AdoHcy is the product of all adenosylmethionine (AdoMet)-dependent biological transmethylations. These reactions have a wide range of products, and are common in all facets of biometabolism. As a product inhibitor, elevated levels of AdoHcy suppress AdoMet-dependent transmethylations. Thus, AdoHcyase is a regulator of biological transmethylation in general. The three-dimensional structure of AdoHcyase complexed with reduced nicotinamide adenine dinucleotide phosphate (NADH) and the inhibitor (1′R, 2′S, 3′R)-9-(2′,3′-dihyroxycyclopenten-1-yl)adenine (DHCeA) was solved by a combination of the crystallographic direct methods program, SnB, to determine the selenium atom substructure and by treating the multiwavelength anomalous diffraction data as a special case of multiple isomorphous replacement. The enzyme architecture resembles that observed for NAD-dependent dehydrogenases, with the catalytic domain and the cofactor binding domain each containing a modified Rossmann fold. The two domains form a deep active site cleft containing the cofactor and bound inhibitor molecule. A comparison of the inhibitor complex of the human enzyme and the structure of the rat enzyme, solved without inhibitor, suggests that a 17° rigid body movement of the catalytic domain occurs upon inhibitor/substrate binding.  相似文献   
108.
109.
Acinetobacter johnsonii has potential use in the remediation of heavy metal-contaminated wastewaters. For metal accumulation, cells must remain intact and metabolically active. The effect of possible accumulation targets, Cd2+, UO2 2+, Cu2+, and Ni2+ on cytoplasmic membrane integrity and polarity was investigated by flow cytometry using a mixture of two fluorescent dyes, propidium iodide and bis-oxonol. The former binds to DNA but cannot cross an intact cytoplasmic membrane, whilst the latter is anionic, lipophilic and stains depolarized cytoplasmic membranes. All four metals permeabilized the cytoplasmic membrane of some cells during the period of exposure. The effects of the metals differed in that Cu2+ and Cd2+ also generated an intermediate population of cells, having intact but depolarized cytoplasmic membranes. Electron microscopy showed corresponding cellular abnormalities following metal exposure. © Rapid Science Ltd. 1998  相似文献   
110.
We examined agonistic interactions between adult females in wild, unprovisioned patas monkeys (Erythrocebus patas) and vervets (Cercopithecus aethiops). The dominance hierarchy of patas is far less clear than that of vervets. Patas had fewer interactions per dyad, fewer dyads with interactions, and a high percentage (18%) of reversals in which lower-ranking females won in agonistic interactions with higher-ranking females. Although the rank ordering of the kinds of interactions patas and vervets displayed is similar, with avoidance being the most frequently observed agonistic response to approaches by other females, patas were chased and supplanted more often than vervets were. The resources over which females were supplanted also differ between species. Supplants over food comprise smaller proportion of total supplants patas than for vervets. Patas appear to feed on less usurpable foods than vervets. We conclude that (1) Erythrocebus and Cercopithecus spp., except C. aethiops, should not be categorized with other Cercopithecinae, and C. aethiops should not be categorized with other Cercopithecus spp. and Erythrocebus, in discussions and analyses of relationships between females within groups and (2) ecological conditions, i.e., usurpability of foods, can override phylogenetic history as the selective pressure determining the nature of female competitive relationships within groups.  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