全文获取类型
收费全文 | 331篇 |
免费 | 39篇 |
出版年
2022年 | 4篇 |
2020年 | 3篇 |
2018年 | 6篇 |
2016年 | 4篇 |
2015年 | 9篇 |
2014年 | 12篇 |
2013年 | 12篇 |
2012年 | 11篇 |
2011年 | 19篇 |
2010年 | 9篇 |
2009年 | 10篇 |
2008年 | 8篇 |
2007年 | 12篇 |
2006年 | 11篇 |
2005年 | 13篇 |
2004年 | 14篇 |
2003年 | 16篇 |
2002年 | 14篇 |
2001年 | 13篇 |
2000年 | 15篇 |
1999年 | 15篇 |
1998年 | 8篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 11篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 10篇 |
1986年 | 6篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 6篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1973年 | 2篇 |
1972年 | 3篇 |
1969年 | 5篇 |
1967年 | 3篇 |
1963年 | 2篇 |
1962年 | 2篇 |
排序方式: 共有370条查询结果,搜索用时 15 毫秒
101.
A proteomics approach to understanding protein ubiquitination 总被引:28,自引:0,他引:28
Peng J Schwartz D Elias JE Thoreen CC Cheng D Marsischky G Roelofs J Finley D Gygi SP 《Nature biotechnology》2003,21(8):921-926
There is a growing need for techniques that can identify and characterize protein modifications on a large or global scale. We report here a proteomics approach to enrich, recover, and identify ubiquitin conjugates from Saccharomyces cerevisiae lysate. Ubiquitin conjugates from a strain expressing 6xHis-tagged ubiquitin were isolated, proteolyzed with trypsin and analyzed by multidimensional liquid chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) for amino acid sequence determination. We identified 1,075 proteins from the sample. In addition, we detected 110 precise ubiquitination sites present in 72 ubiquitin-protein conjugates. Finally, ubiquitin itself was found to be modified at seven lysine residues providing evidence for unexpected diversity in polyubiquitin chain topology in vivo. The methodology described here provides a general tool for the large-scale analysis and characterization of protein ubiquitination. 相似文献
102.
Finley MR Li Y Hua F Lillich J Mitchell KE Ganta S Gilmour RF Freeman LC 《American journal of physiology. Heart and circulatory physiology》2002,283(1):H126-H138
In dogs and in humans, potassium channels formed by ether-a-go-go-related gene 1 protein ERG1 (KCNH2) and KCNQ1 alpha-subunits, in association with KCNE beta-subunits, play a role in normal repolarization and may contribute to abnormal repolarization associated with long QT syndrome (LQTS). The molecular basis of repolarization in horse heart is unknown, although horses exhibit common cardiac arrhythmias and may receive drugs that induce LQTS. In horse heart, we have used immunoblotting and immunostaining to demonstrate the expression of ERG1, KCNQ1, KCNE1, and KCNE3 proteins and RT-PCR to detect KCNE2 message. Peptide N-glycosidase F-sensitive forms of horse ERG1 (145 kDa) and KCNQ1 (75 kDa) were detected. Both ERG1 and KCNQ1 coimmunoprecipitated with KCNE1. Cardiac action potential duration was prolonged by antagonists of either ERG1 (MK-499, cisapride) or KCNQ1/KCNE1 (chromanol 293B). Patch-clamp analysis confirmed the presence of a slow delayed rectifier current. These data suggest that repolarizing currents in horses are similar to those of other species, and that horses are therefore at risk for acquired LQTS. The data also provide unique evidence for coassociation between ERG1 and KCNE1 in cardiac tissue. 相似文献
103.
X-ray crystal structures of half the human papilloma virus E2 binding site: d(GACCGCGGTC).
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The X-ray crystal structure of the DNA decamer d(GACCGCGGTC), containing half the human papilloma virus E2 binding site, has been solved from two crystals grown at different ionic conditions (50 mM MgCl2and 50 mM spermine or 1.56 mM MgCl2and 1.56 mM spermine). Despite the variation in salt concentration, the two DNA structures are in a very similar, A-type DNA conformation, with helical axes curving towards the major groove. Although the salt concentrations do not effect the helical parameters or hydration to a large degree, there is a change in the overall helical curvature; 18 degrees and 31 degrees for the low and high salt structures, respectively. This curvature appears to be sequence specific and biologically relevant when compared with similar DNA structures, including the E2 binding site of a protein-DNA complex. 相似文献
104.
Nucleotide variation in the triosephosphate isomerase (Tpi) locus of Drosophila melanogaster and Drosophila simulans 总被引:3,自引:0,他引:3
Hasson E; Wang IN; Zeng LW; Kreitman M; Eanes WF 《Molecular biology and evolution》1998,15(6):756-769
DNA sequence variation in a 1.1-kb region including the coding portion of
the Tpi locus was examined in 25 homozygous third-chromosome lines of
Drosophila melanogaster, nine lines of Drosophila simulans, and one line of
Drosophila yakuba. Our data show that the widespread allozyme polymorphism
observed in cosmopolitan D. melanogaster is due to a glutamic acid
substitution occurring in a phylogenetically conserved lysine that has been
identified as part of the "hinged-lid" active site of the enzyme. This
observation suggests that the replacement polymorphism may have important
functional consequences. One replacement polymorphism was also observed in
D. simulans, although its functional relevance is more difficult to assess,
since it affects a site that is not strongly conserved. This amino acid
change in D. simulans is associated with a single lineage possessing seven
unique silent substitutions, which may be indicative of balancing selection
or population subdivision. The absence of fixed amino acid differences
between D. melanogaster and D. simulans and only a single difference with
D. yakuba suggests that triose phosphate isomerase is under strong
functional constraint. Silent variation is slightly higher for D.
melanogaster than for D. simulans. Finally, we outline the general lack of
evidence for old balanced polymorphisms at allozyme loci in D.
melanogaster.
相似文献
105.
Mammalian integral membrane receptors are homologous to facilitators and antiporters of yeast, fungi, and eubacteria. 总被引:9,自引:1,他引:8
下载免费PDF全文
![点击此处可从《Protein science : a publication of the Protein Society》网站下载免费的PDF全文](/ch/ext_images/free.gif)
J. Reizer K. Finley D. Kakuda C. L. MacLeod A. Reizer M. H. Saier Jr 《Protein science : a publication of the Protein Society》1993,2(1):20-30
We demonstrate that three integral membrane receptors of mammals--the ecotropic retroviral leukemia receptor (ERR), the human retroviral receptor (HRR), and the T-cell early activator (Tea)--are homologous to a family of transporters specific for amino acids, polyamines, and choline (APC), which catalyze solute uniport, solute:cation symport, or solute:solute antiport in yeast, fungi, and eubacteria. Interestingly, the ERR membrane protein was recently shown to function as a cation:amino acid cotransporter. A binary sequence similarity matrix and an evolutionary tree of the 14 members of this family, illustrating their sequence similarities and divergences, were constructed. Other proteins, including the developmentally controlled GerAII spore germination protein of Bacillus subtilis and the acetylcholine receptor of Drosophila melanogaster gave sequence comparison scores of a sufficiently large magnitude to suggest (but not to establish) a common evolutionary origin with members of the APC family. We report an extended and corrected Tea cDNA sequence and show that the mammalian Tea and ERR encoding genes are differentially expressed in tissues and cell lines. Furthermore, the two mammalian cDNA sequences hybridize with other vertebrate and yeast genomic DNAs under stringent conditions. These observations support the notion that cell surface receptor proteins in mammals are transport proteins that share a common origin with transport proteins of single-celled organisms. Thus, permeases of essential metabolites may function pathologically as viral receptors. 相似文献
106.
Methods for the extraction, isolation and analysis of tissue concentrations of progesterone suitable for studying residue levels from livestock treated with this steroid for the control and synchronization of estrus are presented. The system employs biphasic partitioning for the extraction and silica gel chromatography for the isolation and demonstrates 80 to 90% recovery of 14C-labeled progesterone added as an internal standard. Residue analysis of fat, kidney, liver and muscle tissue samples from ovariectomized non-treated and progesterone treated ewes are compared employing a competitive inhibition radioimmunoassay system which appears to be less specific for progesterone than the gas chromatography-mass spectrometry method employing selective ion monitoring detection. 相似文献
107.
Michael F. A. Finley Sandeep Devata James E. Huettner 《Developmental neurobiology》1999,40(3):271-287
Members of the transforming growth factor‐β superfamily, including bone morphogenetic protein 4 (BMP‐4), have been implicated as regulators of neuronal and glial differentiation. To test for a possible role of BMP‐4 in early mammalian neural specification, we examined its effect on neurogenesis in aggregate cultures of mouse embryonic stem (ES) cells. Compared to control aggregates, in which up to 20% of the cells acquired immunoreactivity for the neuron‐specific antibody TuJ1, aggregates maintained for 8 days in serum‐free medium containing BMP‐4 generated 5‐ to 10‐fold fewer neurons. The action of BMP‐4 was dose dependent and restricted to the fifth through eighth day in suspension. In addition to the reduction in neurons, we observed that ES cell cultures exposed to BMP‐4 contained fewer cells that were immunoreactive for glial fibrillary acidic protein or the HNK‐1 neural antigen. Furthermore, under phase contrast, cultures prepared from BMP‐4–treated aggregates contained a significant proportion of nonneuronal cells with a characteristic flat, elongated morphology. These cells were immunoreactive for antibodies to the intermediate filament protein vimentin; they were rare or absent in control cultures. Treatment with BMP‐4 enhanced the expression of the early mesodermal genes brachyury and tbx6 but had relatively little effect on total cell number or cell death. Coapplication of the BMP‐4 antagonist noggin counteracted the effect of exogenous BMP‐4, but noggin alone had no effect on neuralization in either the absence or presence of retinoids. Collectively, our results suggest that BMP‐4 can overcome the neuralizing action of retinoic acid to enhance mesodermal differentiation of murine ES cells. © 1999 John Wiley & Sons, Inc. J Neurobiol 40: 271–287, 1999 相似文献
108.
The HEAT repeat protein Blm10 regulates the yeast proteasome by capping the core particle 总被引:1,自引:0,他引:1
Schmidt M Haas W Crosas B Santamaria PG Gygi SP Walz T Finley D 《Nature structural & molecular biology》2005,12(4):294-303
Proteasome activity is fine-tuned by associating the proteolytic core particle (CP) with stimulatory and inhibitory complexes. Although several mammalian regulatory complexes are known, knowledge of yeast proteasome regulators is limited to the 19-subunit regulatory particle (RP), which confers ubiquitin-dependence on proteasomes. Here we describe an alternative proteasome activator from Saccharomyces cerevisiae, Blm10. Synthetic interactions between blm10Delta and other mutations that impair proteasome function show that Blm10 functions together with proteasomes in vivo. This large, internally repetitive protein is found predominantly within hybrid Blm10-CP-RP complexes, representing a distinct pool of mature proteasomes. EM studies show that Blm10 has a highly elongated, curved structure. The near-circular profile of Blm10 adapts it to the end of the CP cylinder, where it is properly positioned to activate the CP by opening the axial channel into its proteolytic chamber. 相似文献
109.
The structural genomics initiatives have begun with the aim to create a so-called "basic set library" of protein folds that will be used to improve protein prediction methods. Such a library is thought to require the determination of up to 10,000 new structures, including representative structures of several sequence variants from each protein fold. To meet this goal in a reasonable time frame and cost, automated systems must be utilized to clone and to identify the soluble recombinant proteins contained in multiple genomes. This paper presents such a system, developed using the genome of Caenorhabditis elegans (19,099 genes) as a model eukaryotic organism for structural genomics. This system successfully automates nearly all aspects of recombinant protein expression analysis including subcloning, bacterial growth, recombinant protein expression, protein purification, and scoring protein solubility. 相似文献
110.
The morphology of the statocyst of the Australian crayfish Cherax destructor was examined using scanning electron microscopy. It resembles in general structure, size, and position the statocysts of crayfish described previously, and the size and distribution of the fields of setae on the floor of the capsule are similar but not the same. Over the size range examined, the relationship between the carapace length, the length of the basal antennular segment, the diameter of the statocyst capsule, and the total number of setae are all linear. The number and position of setae on the floor of the statocyst capsule were mapped for animals in two size classes (small, ca. 20 mm; large, ca. 50 mm) to test for changes in their arrangement during growth. The change in the ratio of setal number to statocyst size between the two size classes was about three times greater for the anterior setal field than for the other fields. We propose that differential development of the setal fields may be related to changes in the force-monitoring requirements of the animals as they increase in size, but this remains to be experimentally tested. 相似文献