全文获取类型
收费全文 | 184篇 |
免费 | 11篇 |
国内免费 | 1篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 4篇 |
2020年 | 5篇 |
2019年 | 1篇 |
2018年 | 6篇 |
2017年 | 2篇 |
2016年 | 3篇 |
2015年 | 8篇 |
2014年 | 8篇 |
2013年 | 8篇 |
2012年 | 11篇 |
2011年 | 14篇 |
2010年 | 21篇 |
2009年 | 6篇 |
2008年 | 13篇 |
2007年 | 12篇 |
2006年 | 13篇 |
2005年 | 10篇 |
2004年 | 9篇 |
2003年 | 11篇 |
2002年 | 16篇 |
2001年 | 1篇 |
1998年 | 1篇 |
1997年 | 3篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1981年 | 1篇 |
排序方式: 共有196条查询结果,搜索用时 219 毫秒
21.
Christoffersen TE Aplin M Strom CC Sheikh SP Skott O Busk PK Haunso S Nielsen LB 《American journal of physiology. Heart and circulatory physiology》2006,290(4):H1635-H1641
Both atrial (ANP) and brain (BNP) natriuretic peptide affect development of cardiac hypertrophy and fibrosis via binding to natriuretic peptide receptor (NPR)-A in the heart. A putative clearance receptor, NPR-C, is believed to regulate cardiac levels of ANP and BNP. The renin-angiotensin system also affects cardiac hypertrophy and fibrosis. In this study we examined the expression of genes for the NPRs in rats with pressure-overload cardiac hypertrophy. The ANG II type 1 receptor was blocked with losartan (10 mg.kg(-1).day(-1)) to investigate a possible role of the renin-angiotensin system in regulation of natriuretic peptide and NPR gene expression. The ascending aorta was banded in 84 rats during Hypnorm/Dormicum-isoflurane anesthesia; after 4 wk the rats were randomized to treatment with losartan or placebo. The left ventricle of the heart was removed 1, 2, or 4 wk later. Aortic banding increased left ventricular expression of NPR-A and NPR-C mRNA by 110% (P < 0.001) and 520% (P < 0.01), respectively, after 8 wk; as expected, it also increased the expression of ANP and BNP mRNAs. Losartan induced a slight reduction of left ventricular weight but did not affect the expression of mRNAs for the natriuretic peptides or their receptors. Although increased gene expression does not necessarily convey a higher concentration of the protein, the data suggest that pressure overload is accompanied by upregulation of not only ANP and BNP but also their receptors NPR-A and NPR-C in the left ventricle. 相似文献
22.
23.
Heath E Brown WA Jensen SR Bratty MP 《Journal of industrial microbiology & biotechnology》2006,33(3):197-207
The biodegradation of chlorinated alkanes was studied under oxic conditions with the objective of identifying favorable and
unfavorable intramolecular chlorination sequences with respect to the enzymes studied. Several dehalogenating bacterial strains
were screened for their ability to degrade middle-chain polychlorinated alkanes as well as a commercial mixture. Of the organisms
tested, the most promising was Pseudomonas sp. strain 273, which possesses an oxygenolytic dehalogenase. The effects of carbon chain length (C6–C16), halogen position, and overall chlorine content (14–61% w/w) were examined using both commercially available compounds and
molecules synthesized in our laboratory. The effects of co-substrates, solvents, and inducing agents were also studied. The
results with pure chlorinated alkanes showed that the relative positions of the chlorine atoms strongly influenced the total
amount of dehalogenation achieved. The greatest dehalogenation yields were associated with terminally chlorinated alkanes.
The α- and α,ω-chlorinated compounds yielded similar results. Vicinal chlorination had the most dramatic impact on degradation.
When present on both ends or at the center of the molecule, no dehalogenation was detected. Although partial dehalogenation
of 1,2-dichlorodecane was observed, it was likely due to a combination of β-oxidation and an abiotic mechanism. Cereclor S52
was appreciably dehalogenated in shake flasks only when 1,10-dichlorodecane was present as a co-substrate and after increasing
the oil surface area through mechanical emulsification, demonstrating the importance of abiotic factors in degrading commercial
polychlorinated alkane mixtures. 相似文献
24.
Effects of salinity on hard clam (Mercenaria mercenaria) defense parameters and QPX disease dynamics
QPX (Quahog Parasite Unknown) is a protistan parasite affecting hard clams (Mercenaria mercenaria) along the Northeast coast of the United States. The fact that QPX disease epizootics are usually observed in field sites with high salinities led to the general assumption that salinity represents an important factor for disease distribution. This study was designed to investigate the effect of salinity on QPX disease development as well as constitutive and QPX-induced defense factors in M. mercenaria. Naïve and QPX-infected (both experimentally and naturally) clams were submitted to 17 and 30 psu for 4 months. Standard and QPX-specific cellular and humoral defense parameters were assessed after 2 and 4 months. These included total and differential hemocyte counts, reactive oxygen species production, phagocytic activity of hemocytes, lysozyme concentration in plasma, anti-QPX activity in plasma and resistance of hemocytes to cytotoxic QPX extracellular products. Results demonstrated higher QPX-associated mortality in naturally infected clams maintained at high salinity compared to those held at 17 psu. Our findings also showed an increase in mortality following experimental challenge with QPX in clams submitted to 30 psu but not in those held at 17 psu. Constitutive clam defense factors and the response to QPX challenge were also affected by salinity. QPX challenge caused significant but transitory changes in hemolymph parameters that were obvious at 2 months but disappeared at 4 months. Overall, our results show that salinity modulates clam immunity and the progress of QPX disease although its impact appears secondary as compared to findings we reported earlier for temperature. 相似文献
25.
ML Zupancic BL Cantarel Z Liu EF Drabek KA Ryan S Cirimotich C Jones R Knight WA Walters D Knights EF Mongodin RB Horenstein BD Mitchell N Steinle S Snitker AR Shuldiner CM Fraser 《PloS one》2012,7(8):e43052
Obesity has been linked to the human gut microbiota; however, the contribution of gut bacterial species to the obese phenotype remains controversial because of conflicting results from studies in different populations. To explore the possible dysbiosis of gut microbiota in obesity and its metabolic complications, we studied men and women over a range of body mass indices from the Old Order Amish sect, a culturally homogeneous Caucasian population of Central European ancestry. We characterized the gut microbiota in 310 subjects by deep pyrosequencing of bar-coded PCR amplicons from the V1-V3 region of the 16S rRNA gene. Three communities of interacting bacteria were identified in the gut microbiota, analogous to previously identified gut enterotypes. Neither BMI nor any metabolic syndrome trait was associated with a particular gut community. Network analysis identified twenty-two bacterial species and four OTUs that were either positively or inversely correlated with metabolic syndrome traits, suggesting that certain members of the gut microbiota may play a role in these metabolic derangements. 相似文献
26.
Bringans S Eriksen S Kendrick T Gopalakrishnakone P Livk A Lock R Lipscombe R 《Proteomics》2008,8(5):1081-1096
Venoms have evolved over millions of years into potent cocktails of bioactive peptides and proteins. These compounds can be of great value to the pharmaceutical industry for numerous clinical applications. In this study, a novel proteomic - bioinformatic approach was utilised, where chromatography followed by gel electrophoresis was utilised to separate the venom peptides/proteins of Heterometrus longimanus (Asian black scorpion). Purified peptides were analysed by tandem mass spectrometry, de novo sequenced and then homology matched against known peptides in the Swiss-Prot protein database. Numerous potentially biologically active peptide matches were discovered, and a simple scoring system applied to putatively assign functions to the peptides. As a validation of this approach, the functional composition of the experimentally derived proteome is similar to that of other scorpions, and contains a potent mix of toxins, antimicrobials and ionic channel inhibitors. 相似文献
27.
Leisner C Loeth N Lamberth K Justesen S Sylvester-Hvid C Schmidt EG Claesson M Buus S Stryhn A 《PloS one》2008,3(2):e1678
Background
Cytotoxic T Lymphocytes (CTL) recognize complexes of peptide ligands and Major Histocompatibility Complex (MHC) class I molecules presented at the surface of Antigen Presenting Cells (APC). Detection and isolation of CTL''s are of importance for research on CTL immunity, and development of vaccines and adoptive immune therapy. Peptide-MHC tetramers have become important reagents for detection and enumeration of specific CTL''s. Conventional peptide-MHC-tetramer production involves recombinant MHC production, in vitro refolding, biotinylation and tetramerization; each step followed by various biochemical steps such as chromatographic purification, concentration etc. Such cumbersome production protocols have limited dissemination and restricted availability of peptide-MHC tetramers effectively precluding large-scale screening strategies involving many different peptide-MHC tetramers.Methodology/Principal Findings
We have developed an approach whereby any given tetramer specificity can be produced within 2 days with very limited effort and hands-on time. The strategy is based on the isolation of correctly oxidized, in vivo biotinylated recombinant MHC I heavy chain (HC). Such biotinylated MHC I HC molecules can be refolded in vitro, tetramerized with streptavidin, and used for specific T cell staining-all in a one-pot reaction without any intervening purification steps.Conclusions/Significance
We have developed an efficient “one-pot, mix-and-read” strategy for peptide-MHC tetramer generation, and demonstrated specific T cell straining comparable to a commercially available MHC-tetramer. Here, seven peptide-MHC tetramers representing four different human MHC (HLA) class I proteins have been generated. The technique should be readily extendable to any binding peptide and pre-biotinylated MHC (at this time we have over 40 different pre-biotinylated HLA proteins). It is simple, robust, and versatile technique with a very broad application potential as it can be adapted both to small- and large-scale production of one or many different peptide-MHC tetramers for T cell isolation, or epitope screening. 相似文献28.
Valiyaveettil M Bentley AA Gursahaney P Hussien R Chakravarti R Kureishy N Prag S Adams JC 《The Journal of cell biology》2008,182(4):727-739
The evolutionarily conserved kelch-repeat protein muskelin was identified as an intracellular mediator of cell spreading. We discovered that its morphological activity is controlled by association with RanBP9/RanBPM, a protein involved in transmembrane signaling and a conserved intracellular protein complex. By subcellular fractionation, endogenous muskelin is present in both the nucleus and the cytosol. Muskelin subcellular localization is coregulated by its C terminus, which provides a cytoplasmic restraint and also controls the interaction of muskelin with RanBP9, and its atypical lissencephaly-1 homology motif, which has a nuclear localization activity which is regulated by the status of the C terminus. Transient or stable short interfering RNA–based knockdown of muskelin resulted in protrusive cell morphologies with enlarged cell perimeters. Morphology was specifically restored by complementary DNAs encoding forms of muskelin with full activity of the C terminus for cytoplasmic localization and RanBP9 binding. Knockdown of RanBP9 resulted in equivalent morphological alterations. These novel findings identify a role for muskelin–RanBP9 complex in pathways that integrate cell morphology regulation and nucleocytoplasmic communication. 相似文献
29.
30.
Lijun Ma Yuan Zhang David J. Lohman Niklas Wahlberg Fangzhou Ma Soren Nylin Niklas Janz Masaya Yago Kwaku Aduse-Poku Djunijanti Peggie Min Wang Peng Zhang Houshuai Wang 《Systematic Entomology》2020,45(4):924-934
Recent advances in obtaining reduced representation libraries for next-generation sequencing permit phylogenomic analysis of species-rich, recently diverged taxa. In this study, we performed sequence capture with homemade PCR-generated probes to study diversification among closely related species in a large insect genus to examine the utility of this method. We reconstructed the phylogeny of Neptis Fabricius, a large and poorly studied nymphalid butterfly genus distributed throughout the Old World. We inferred relationships among 108 Neptis samples using 89 loci totaling up to 84 519 bp per specimen. Our taxon sample focused on Palearctic, Oriental and Australasian species, but included 8 African species and outgroups from 5 related genera. Maximum likelihood and Bayesian analyses yielded identical trees with full support for almost all nodes. We confirmed that Neptis is not monophyletic because Lasippa heliodore (Fabricius) and Phaedyma amphion (Linnaeus) are nested within the genus, and we redefine species groups for Neptis found outside of Africa. The statistical support of our results demonstrates that the probe set we employed is useful for inferring phylogenetic relationships among Neptis species and likely has great value for intrageneric phylogenetic reconstruction of Lepidoptera. Based on our results, we revise the following two taxa: Neptis heliodore comb. rev. and Neptis amphion comb. rev. 相似文献