全文获取类型
收费全文 | 1084篇 |
免费 | 52篇 |
国内免费 | 1篇 |
出版年
2024年 | 2篇 |
2023年 | 7篇 |
2022年 | 19篇 |
2021年 | 42篇 |
2020年 | 20篇 |
2019年 | 28篇 |
2018年 | 28篇 |
2017年 | 28篇 |
2016年 | 48篇 |
2015年 | 55篇 |
2014年 | 67篇 |
2013年 | 88篇 |
2012年 | 114篇 |
2011年 | 87篇 |
2010年 | 65篇 |
2009年 | 38篇 |
2008年 | 48篇 |
2007年 | 61篇 |
2006年 | 53篇 |
2005年 | 53篇 |
2004年 | 39篇 |
2003年 | 37篇 |
2002年 | 20篇 |
2001年 | 11篇 |
2000年 | 7篇 |
1999年 | 8篇 |
1998年 | 6篇 |
1997年 | 5篇 |
1996年 | 8篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 1篇 |
1992年 | 6篇 |
1991年 | 2篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有1137条查询结果,搜索用时 62 毫秒
101.
Arun Kumar Tripathi Rajendra Singh Bhakuni Shikha Upadhyay Rashmi Gaur 《Insect Science》2011,18(2):189-194
Abstract Artemisia annua (Asteraceae) is well known for its antimalarial activities due to presence of the compound artemisinin. We isolated a methoxy coumarin from the stem part of A. annua and confirmed its identity as scopoletin through mass spectral data. The structure was established from 1H‐nuclear magnetic resonance (NMR), 13C‐NMR. The compound scopoletin was evaluated for its feeding deterrence and growth inhibitory potential against a noxious lepidopteran insect, Spilartctia obliqua Walker. Scopoletin gave FD50 (feeding deterrence of 50%) value of 96.7 μg/g diet when mixed into artificial diet. S. obliqua larvae (12‐day‐old) exposed to the highest concentration (250 μg/g diet) of scopoletin showed 77.1% feeding‐deterrence. In a growth inhibitory assay, scopoletin provided 116.9% growth inhibition at the highest dose of 250 μg/g diet with a GI50 (growth inhibition of 50%) value of 20.9 μg/g diet. Statistical analysis showed a concentration‐dependent dose response relationship toward both feeding deterrent and growth inhibitory activities. Artemisinin is found mainly in the leaves of A. annua and not in the stems, which are typically discarded as waste. Therefore identification of scopoletin in stems of A. annua may be important as a source of this material for pest control. 相似文献
102.
103.
Thangaraj K Sridhar V Kivisild T Reddy AG Chaubey G Singh VK Kaur S Agarawal P Rai A Gupta J Mallick CB Kumar N Velavan TP Suganthan R Udaykumar D Kumar R Mishra R Khan A Annapurna C Singh L 《Human genetics》2005,116(6):507-517
Length variation in the human mtDNA intergenic region between the cytochrome oxidase II (COII) and tRNA lysine (tRNAlys) genes has been widely studied in world populations. Specifically, Austronesian populations of the Pacific and Austro-Asiatic populations of southeast Asia most frequently carry the 9-bp deletion in that region implying their shared common ancestry in haplogroup B. Furthermore, multiple independent origins of the 9-bp deletion at the background of other mtDNA haplogroups has been shown in populations of Africa, Europe, Australia, and India. We have analyzed 3293 Indian individuals belonging to 58 populations, representing different caste, tribal, and religious groups, for the length variation in the 9-bp motif. The 9-bp deletion (one copy) and insertion (three copies) alleles were observed in 2.51% (2.15% deletion and 0.36% insertion) of the individuals. The maximum frequency of the deletion (45.8%) was observed in the Nicobarese in association with the haplogroup B5a D-loop motif that is common throughout southeast Asia. The low polymorphism in the D-loop sequence of the Nicobarese B5a samples suggests their recent origin and a founder effect, probably involving migration from southeast Asia. Interestingly, none of the 302 (except one Munda sample, which has 9-bp insertion) from Mundari-speaking Austro-Asiatic populations from the Indian mainland showed the length polymorphism of the 9-bp motif, pointing either to their independent origin from the Mon-Khmeric-speaking Nicobarese or to an extensive admixture with neighboring Indo-European-speaking populations. Consistent with previous reports, the Indo-European and Dravidic populations of India showed low frequency of the 9-bp deletion/insertion. More than 18 independent origins of the deletion or insertion mutation could be inferred in the phylogenetic analysis of the D-loop sequences. 相似文献
104.
Leung W Iyengar R Leimig T Holladay MS Houston J Handgretinger R 《Cancer immunology, immunotherapy : CII》2005,54(4):389-394
Infection, disease relapse, graft failure, and graft-versus-host disease (GVHD) are significant adverse events associated with allogeneic bone marrow transplantation. Donor natural killer (NK) cells may be an ideal cell type for prevention or treatment of all these adverse events. Therefore, we investigated the phenotype and function of human NK cells purified by using a clinical-scale immunomagnetic method. We found that the NK cell purification procedures did not adversely affect the expression of killer cell immunoglobulin-like receptors, adhesion molecules, intracellular cytokines, perforin, and granzyme B. Purified NK cells had extensive proliferative capacity and potent antitumor activity when assessed using an immunodeficient mouse model. While all mice transplanted with unpurified mononuclear cells developed GVHD, none of the mice transplanted with purified NK cells did. NK cells were highly susceptible to lysis by antithymocyte globulin (ATG), whereas G-CSF had a minimal effect on their natural cytotoxicity. These results support future clinical investigation of the use of purified NK cells for adoptive immunotherapy in the absence of ATG. 相似文献
105.
Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Soosairajah J Maiti S Wiggan O Sarmiere P Moussi N Sarcevic B Sampath R Bamburg JR Bernard O 《The EMBO journal》2005,24(3):473-486
Slingshot (SSH) phosphatases and LIM kinases (LIMK) regulate actin dynamics via a reversible phosphorylation (inactivation) of serine 3 in actin-depolymerizing factor (ADF) and cofilin. Here we demonstrate that a multi-protein complex consisting of SSH-1L, LIMK1, actin, and the scaffolding protein, 14-3-3zeta, is involved, along with the kinase, PAK4, in the regulation of ADF/cofilin activity. Endogenous LIMK1 and SSH-1L interact in vitro and co-localize in vivo, and this interaction results in dephosphorylation and downregulation of LIMK1 activity. We also show that the phosphatase activity of purified SSH-1L is F-actin dependent and is negatively regulated via phosphorylation by PAK4. 14-3-3zeta binds to phosphorylated slingshot, decreases the amount of slingshot that co-sediments with F-actin, but does not alter slingshot activity. Here we define a novel ADF/cofilin phosphoregulatory complex and suggest a new mechanism for the regulation of ADF/cofilin activity in mediating changes to the actin cytoskeleton. 相似文献
106.
Mythili MD Vyas R Patra SS Nair SC Akila G Sujatha R Gunasekaran S 《Journal of medical primatology》2005,34(1):35-40
The present study is aimed at determining some haematological and biochemical parameters in the wild Indian bonnet monkeys as also the microscopic and ultrastructural characteristics of their pancreatic islets. Adult wild Indian bonnet monkeys (Macaca radiata radiata) of both sexes weighing between 2.5 and 4 kg were used in these experiments. Their platelet, reticulocyte and total leukocyte counts and the blood concentrations of hemoglobin and plasma proteins and the serum concentrations of aspartate amino transferase, alanine amino transferase and calcium are similar to the values reported for M. mulatta. Plasma glucose is lower when compared with reported values of M. mulatta and M. fascicularis. Insulin levels are comparable with those of M. mulatta and M. nigra. Histology of islets is similar to that of humans. Ovoid cell collections of islet cells are scattered throughout the pancreas. Ultrastructure of A, B and D cells is similar to humans. These findings suggest that this relatively underutilized macaques may be a suitable model for biomedical research. 相似文献
107.
Ding XZ Bhattacharjee A Nikolich MP Paulsen IT Myers G Seshadri R L Hoover D 《Protein expression and purification》2005,40(1):134-141
Brucella, an aerobic, nonsporeforming, nonmotile Gram-negative coccobacillus, is a NIH/CDC category B bioterror threat agent that causes incapacitating human illness. Medical defense against the bioterror threat posed by Brucella would be strengthened by development of a human vaccine and improved diagnostic tests. Central to advancement of these goals is discovery of bacterial constituents that are immunogenic or antigenic for humans. Outer membrane proteins (OMPs) are particularly attractive for this purpose. In this study, we cloned, expressed, and purified seven predicted OMPs of Brucella suis. The recombinant proteins were fused with 6-His and V5 epitope tags at their C termini to facilitate detection and purification. The B. suis surface genes were PCR synthesized based on their ORF sequences and directly cloned into an entry vector. The recombinant entry constructs were propagated in TOP 10 cells, recombined into a destination vector, pET-DEST42, then transformed into Escherichia coli BL21 cells for IPTG-induced protein expression. The expressed recombinant proteins were confirmed with Western blot analysis using anti-6-His antibody conjugated with alkaline phosphatase. These B. suis OMPs were captured and purified using a HisGrab plate. The purified recombinant proteins were examined for their binding activity with antiserum. Serum derived from a rabbit immunized intramuscularly with dialyzed cell lysate of Brucella rough mutant WRR51. The OMPs were screened using the rabbit antiserum and purified IgG. The results suggested that recombinant B. suis OMPs were successfully cloned, expressed and purified. Some of the expressed OMPs showed high binding activity with immunized rabbit antiserum. 相似文献
108.
Trivedi OA Arora P Vats A Ansari MZ Tickoo R Sridharan V Mohanty D Gokhale RS 《Molecular cell》2005,17(5):631-643
Mycobacterium tuberculosis cell envelope is a treasure house of biologically active lipids of fascinating molecular architecture. Although genetic studies have alluded to an array of genes in biosynthesis of complex lipids, their mechanistic, structural, and biochemical principles have not been investigated. Here, we have dissected the molecular logic underlying the biosynthesis of a virulence lipid phthiocerol dimycocerosate (PDIM). Cell-free reconstitution studies demonstrate that polyketide synthases, which are usually involved in the biosynthesis of secondary metabolites, are responsible for generating complex lipids in mycobacteria. We show that PapA5 protein directly transfers the protein bound mycocerosic acid analogs on phthiocerol to catalyze the final esterification step. Based on precise identification of biological functions of proteins from Pps cluster, we have rationally produced a nonmethylated variant of mycocerosate esters. Apart from elucidating mechanisms that generate chemical heterogeneity with PDIMs, this study also presents an attractive approach to explore host-pathogen interactions by altering mycobacterial surface coat. 相似文献
109.
Using a data set of aligned protein domain superfamilies of known three-dimensional structure, we compared the location of interdomain interfaces on the tertiary folds between members of distantly related protein domain superfamilies. The data set analyzed is comprised of interdomain interfaces, with domains occurring within a polypeptide chain and those between two polypeptide chains. We observe that, in general, the interfaces between protein domains are formed entirely in different locations on the tertiary folds in such pairs. This variation in the location of interface happens in protein domains involved in a wide range of functions, such as enzymes, adapters, and domains that bind protein ligands, or cofactors. While basic biochemical functionality is preserved at the domain superfamily level, the effect of biochemical function on protein assemblies is different in these protein domains related by superfamily. The divergence between proteins, in most cases, is coupled with domain recruitment, with different modes of interaction with the recruited domain. This is in complete contrast to the observation that in closely related homologous protein domains, almost always the interaction interfaces are topologically equivalent. In a small subset of interacting domains within proteins related by remote homology, we observe that the relative positioning of domains with respect to one another is preserved. Based on the analysis of multidomain proteins of known or unknown structure, we suggest that variation in protein-protein interactions in members within a superfamily could serve as diverging points in otherwise parallel metabolic or signaling pathways. We discuss a few representative cases of diverging pathways involving domains in a superfamily. 相似文献
110.