全文获取类型
收费全文 | 224篇 |
免费 | 12篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 7篇 |
2020年 | 6篇 |
2019年 | 2篇 |
2018年 | 3篇 |
2017年 | 3篇 |
2016年 | 9篇 |
2015年 | 8篇 |
2014年 | 10篇 |
2013年 | 19篇 |
2012年 | 12篇 |
2011年 | 27篇 |
2010年 | 9篇 |
2009年 | 4篇 |
2008年 | 12篇 |
2007年 | 14篇 |
2006年 | 10篇 |
2005年 | 10篇 |
2004年 | 9篇 |
2003年 | 7篇 |
2002年 | 14篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 1篇 |
1995年 | 6篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1988年 | 2篇 |
1985年 | 2篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 1篇 |
排序方式: 共有236条查询结果,搜索用时 31 毫秒
81.
Zefeng Zhang Mary E. Cogswell Cathleen Gillespie Jing Fang Fleetwood Loustalot Shifan Dai Alicia L. Carriquiry Elena V. Kuklina Yuling Hong Robert Merritt Quanhe Yang 《PloS one》2013,8(10)
Objectives
Studies indicate high sodium and low potassium intake can increase blood pressure suggesting the ratio of sodium-to-potassium may be informative. Yet, limited studies examine the association of the sodium-to-potassium ratio with blood pressure and hypertension.Methods
We analyzed data on 10,563 participants aged ≥20 years in the 2005–2010 National Health and Nutrition Examination Survey who were neither taking anti-hypertensive medication nor on a low sodium diet. We used measurement error models to estimate usual intakes, multivariable linear regression to assess their associations with blood pressure, and logistic regression to assess their associations with hypertension.Results
The average usual intakes of sodium, potassium and sodium-to-potassium ratio were 3,569 mg/d, 2,745 mg/d, and 1.41, respectively. All three measures were significantly associated with systolic blood pressure, with an increase of 1.04 mmHg (95% CI, 0.27–1.82) and a decrease of 1.24 mmHg (95% CI, 0.31–2.70) per 1,000 mg/d increase in sodium or potassium intake, respectively, and an increase of 1.05 mmHg (95% CI, 0.12–1.98) per 0.5 unit increase in sodium-to-potassium ratio. The adjusted odds ratios for hypertension were 1.40 (95% CI, 1.07–1.83), 0.72 (95% CI, 0.53–0.97) and 1.30 (95% CI, 1.05–1.61), respectively, comparing the highest and lowest quartiles of usual intake of sodium, potassium or sodium-to-potassium ratio.Conclusions
Our results provide population-based evidence that concurrent higher sodium and lower potassium consumption are associated with hypertension. 相似文献82.
Reinholdt LG Ding Y Gilbert GJ Gilbert GT Czechanski A Solzak JP Roper RJ Johnson MT Donahue LR Lutz C Davisson MT 《Mammalian genome》2011,22(11-12):685-691
Ts65Dn is a mouse model of Down syndrome: a syndrome that results from chromosome (Chr) 21 trisomy and is associated with congenital defects, cognitive impairment, and ultimately Alzheimer's disease. Ts65Dn mice have segmental trisomy for distal mouse Chr 16, a region sharing conserved synteny with human Chr 21. As a result, this strain harbors three copies of over half of the human Chr 21 orthologs. The trisomic segment of Chr 16 is present as a translocation chromosome (Mmu17(16)), with breakpoints that have not been defined previously. To molecularly characterize the Chrs 16 and 17 breakpoints on the translocation chromosome in Ts65Dn mice, we used a selective enrichment and high-throughput paired-end sequencing approach. Analysis of paired-end reads flanking the Chr 16, Chr 17 junction on Mmu17(16) and de novo assembly of the reads directly spanning the junction provided the precise locations of the Chrs 16 and 17 breakpoints at 84,351,351 and 9,426,822?bp, respectively. These data provide the basis for low-cost, highly efficient genotyping of Ts65Dn mice. More importantly, these data provide, for the first time, complete characterization of gene dosage in Ts65Dn mice. 相似文献
83.
Wolf S Haase-Kohn C Lenk J Hoppmann S Bergmann R Steinbach J Pietzsch J 《Amino acids》2011,41(4):809-820
Data concerning the pathophysiological role of extracellular S100A4, a member of the multigenic family of Ca2+-modulated S100 proteins, and its interaction with the receptor for advanced glycation endproducts (RAGE) or other putative
receptors in tumorigenesis, metastasis, and inflammatory processes in vivo are scarce. One reason is the shortage of suitable
radiotracer methods. We report a novel methodology using recombinant human S100A4 as potential probe for molecular imaging
and functional characterization of this interaction. Therefore, human S100A4 was cloned as GST fusion protein in the bacterial
expression vector pGEX-6P-1 and expressed in E. coli strain BL21. Purified recombinant human S100A4 was radiolabeled with the positron emitter fluorine-18 (18F) by conjugation with N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB). The radioligand [18F]fluorobenzoyl-S100A4 (18F-S100A4) was used in cell binding experiments in RAGE-bearing human melanoma cells and endothelial cells in vitro, and in
both biodistribution experiments and small animal positron emission tomography (PET) studies in normal rats in vivo. The cellular
association and tissue-specific distribution of 18F-S100A4 in vitro and in vivo correlated well with the protein expression and anatomical localization of RAGE, e.g., in the
vascular system and in lung. Compared to other S100 RAGE radioligands, the overall findings of this study indicate that extracellular
S100A4 in vivo shows only a moderate interaction with RAGE and, furthermore, exhibits a substantially faster metabolic degradation.
On the other hand, the approach allows the use of quantitative small animal PET and provides a novel probe to both delineate
functional expression and differentiate multiligand interaction of RAGE under normal and pathophysiological conditions in
rodent models of disease. 相似文献
84.
Hernandez JA Phillips AH Erbil WK Zhao D Demuez M Zeymer C Pelton JG Wemmer DE Rubio LM 《The Journal of biological chemistry》2011,286(8):6321-6328
NafY participates in the final steps of nitrogenase maturation, having a dual role as iron-molybdenum cofactor (FeMo-co) carrier and as chaperone to the FeMo-co-deficient apo-NifDK (apo-dinitrogenase). NafY contains an N-terminal domain of unknown function (n-NafY) and a C-terminal domain (core-NafY) necessary for FeMo-co binding. We show here that n-NafY and core-NafY have very weak interactions in intact NafY. The NMR structure of n-NafY reveals that it belongs to the sterile α-motif (SAM) family of domains, which are frequently involved in protein-protein interactions. The presence of a SAM domain in NafY was unexpected and could not be inferred from its amino acid sequence. Although SAM domains are very commonly found in eukaryotic proteins, they have rarely been identified in prokaryotes. The n-NafY SAM domain binds apo-NifDK. As opposed to full-length NafY, n-NafY impaired FeMo-co insertion when present in molar excess relative to FeMo-co and apo-NifDK. The implications of these observations are discussed to offer a plausible mechanism of FeMo-co insertion. NafY domain structure, molecular tumbling, and interdomain motion, as well as NafY interaction with apo-NifDK are consistent with the function of NafY in FeMo-co delivery to apo-NifDK. 相似文献
85.
Shah AH Cianciola NL Mills JL Sönnichsen FD Carlin C 《The Journal of cell biology》2007,179(5):965-980
The small guanosine triphosphatase Rab7 regulates late endocytic trafficking. Rab7-interacting lysosomal protein (RILP) and oxysterol-binding protein–related protein 1L (ORP1L) are guanosine triphosphate (GTP)–Rab7 effectors that instigate minus end–directed microtubule transport. We demonstrate that RILP and ORP1L both interact with the group C adenovirus protein known as receptor internalization and degradation α (RIDα), which was previously shown to clear the cell surface of several membrane proteins, including the epidermal growth factor receptor and Fas (Carlin, C.R., A.E. Tollefson, H.A. Brady, B.L. Hoffman, and W.S. Wold. 1989. Cell. 57:135–144; Shisler, J., C. Yang, B. Walter, C.F. Ware, and L.R. Gooding. 1997. J. Virol. 71:8299–8306). RIDα localizes to endocytic vesicles but is not homologous to Rab7 and is not catalytically active. We show that RIDα compensates for reduced Rab7 or dominant-negative (DN) Rab7(T22N) expression. In vitro, Cu2+ binding to RIDα residues His75 and His76 facilitates the RILP interaction. Site-directed mutagenesis of these His residues results in the loss of RIDα–RILP interaction and RIDα activity in cells. Additionally, expression of the RILP DN C-terminal region hinders RIDα activity during an acute adenovirus infection. We conclude that RIDα coordinates recruitment of these GTP-Rab7 effectors to compartments that would ordinarily be perceived as early endosomes, thereby promoting the degradation of selected cargo. 相似文献
86.
Structure and biological activities of beta toxin from Staphylococcus aureus 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Journal of bacteriology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Huseby M Shi K Brown CK Digre J Mengistu F Seo KS Bohach GA Schlievert PM Ohlendorf DH Earhart CA 《Journal of bacteriology》2007,189(23):8719-8726
Beta toxin is a neutral sphingomyelinase secreted by certain strains of Staphylococcus aureus. This virulence factor lyses erythrocytes in order to evade the host immune system as well as scavenge nutrients. The structure of beta toxin was determined at 2.4-Å resolution using crystals that were merohedrally twinned. This structure is similar to that of the sphingomyelinases of Listeria ivanovii and Bacillus cereus. Beta toxin belongs to the DNase I folding superfamily; in addition to sphingomyelinases, the proteins most structurally related to beta toxin include human endonuclease HAP1, Escherichia coli endonuclease III, bovine pancreatic DNase I, and the endonuclease domain of TRAS1 from Bombyx mori. Our biological assays demonstrated for the first time that beta toxin kills proliferating human lymphocytes. Structure-directed active site mutations show that biological activities, including hemolysis and lymphotoxicity, are due to the sphingomyelinase activity of the enzyme. 相似文献
87.
Ma Cathleen Duan Chenyang Jiang Yuan Nagle Michael Peremyslova Ekaterina Goddard Amanda Strauss Steven H. 《In vitro cellular & developmental biology. Plant》2022,58(6):853-864
In Vitro Cellular & Developmental Biology - Plant - To enhance the sensitivity of an ongoing Genome Wide Association Study (GWAS) for in vitro shoot regeneration and genetic transformation, a... 相似文献
88.
89.
Anuj Srivastava Vivek M Philip Ian Greenstein Lucy B Rowe Mary Barter Cathleen Lutz Laura G Reinholdt 《BMC genomics》2014,15(1)
Background
Transgenesis by random integration of a transgene into the genome of a zygote has become a reliable and powerful method for the creation of new mouse strains that express exogenous genes, including human disease genes, tissue specific reporter genes or genes that allow for tissue specific recombination. Nearly 6,500 transgenic alleles have been created by random integration in embryos over the last 30 years, but for the vast majority of these strains, the transgene insertion sites remain uncharacterized.Results
To obtain a complete understanding of how insertion sites might contribute to phenotypic outcomes, to more cost effectively manage transgenic strains, and to fully understand mechanisms of instability in transgene expression, we’ve developed methodology and a scoring scheme for transgene insertion site discovery using high throughput sequencing data.Conclusions
Similar to other molecular approaches to transgene insertion site discovery, high-throughput sequencing of standard paired-end libraries is hindered by low signal to noise ratios. This problem is exacerbated when the transgene consists of sequences that are also present in the host genome. We’ve found that high throughput sequencing data from mate-pair libraries are more informative when compared to data from standard paired end libraries. We also show examples of the genomic regions that harbor transgenes, which have in common a preponderance of repetitive sequences.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-367) contains supplementary material, which is available to authorized users. 相似文献90.
Stephan Fricke Cathleen Pfefferkorn Doris Wolf Sina Riemschneider Janine Kohlschmidt Nadja Hilger Christiane Fueldner Jens Knauer Ulrich Sack Frank Emmrich J?rg Lehmann 《PloS one》2014,9(12)
Starting point for the present work was the assumption that the cell line MuMac-E8 represents a murine cell population with stem cell properties. Preliminary studies already pointed to the expression of stem-cell associated markers and a self-regenerative potential of the cells. The cell line MuMac-E8 should be examined for their differential stage within stem cell hierarchy. MuMac-E8 cells were derived from a chimeric mouse model of arthritis. It could be shown that MuMac-E8 cells express mRNA of some genes associated with pluripotent stem cells (Nanog, Nucleostemin), of genes for hematopoietic markers (EPCR, Sca-1, CD11b, CD45), for the mesenchymal marker CD105 and of genes for the neural markers Pax-6 and Ezrin. In methylcellulose and May-Grünwald-Giemsa staining, hematopoietic colonies were obtained but the hematopoietic system of lethally irradiated mice could not be rescued. Osteogenic differentiation was not detectable. Thus, it became evident that MuMac-E8 represents not a stem cell line. However, MuMac-E8 cells expressed several myeloid surface markers (i.e. CD11b, F4/80, CD14, CD64), showed phagocytosis and is capable of producing nitric oxide. Thus, this cell line seems to be arrested an advanced stage of myeloid differentiation. Adherence data measured by impedance-based real-time cell analysis together with cell morphology data suggested that MuMac-E8 represents a new macrophage precursor cell line exhibiting weak adherence. This cell line is suitable as an in-vitro model for testing of macrophage functions. Moreover, it might be also useful for differentiation or reprogramming studies. 相似文献