全文获取类型
收费全文 | 103篇 |
免费 | 9篇 |
出版年
2017年 | 1篇 |
2016年 | 2篇 |
2015年 | 3篇 |
2014年 | 2篇 |
2013年 | 5篇 |
2012年 | 1篇 |
2011年 | 1篇 |
2010年 | 5篇 |
2009年 | 4篇 |
2008年 | 4篇 |
2007年 | 4篇 |
2006年 | 5篇 |
2005年 | 6篇 |
2004年 | 4篇 |
2003年 | 3篇 |
2002年 | 6篇 |
2001年 | 1篇 |
2000年 | 5篇 |
1999年 | 3篇 |
1998年 | 7篇 |
1995年 | 1篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 6篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1978年 | 1篇 |
1977年 | 1篇 |
排序方式: 共有112条查询结果,搜索用时 15 毫秒
1.
Steven L. Gonias Salvatore V. Pizzo 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,678(2):268-274
Clearance studies were performed in mice using α2-macroglobulin (α2M), α2M-trypsin comlex and α2M-CH3NH2 complex. All three species were incubated with cis-dichlorodiamine platinum(II) (cis-DDPt) at concentrations between 9.0 μM and 1.67 mM for 4 h and then dialyzed. The clearance rate of native α2M was unchanged following incubation with cis-DDPt. α2M-trypsin and α2M-CH3NH2 cleared rapidly from the ciruculation; however, reaction with cis-DDPt significantly decreased the plasma elimination rate of both complexes. Non-denaturing gel electrophoresis and α2M activity assays demonstrated relative stability following incubations with cis-DDPt which markedly altered clearance. Evidence for cis-DDPt crosslinking of α2M subunits was obtained: however, whether this crosslinking is involved in altered clearance remains undetermined. Iodoacetamide treatment of α2M did not duplicate the effect of cis-DDPton α2M clearance, nor did it inhibit the effect of cis-DDPt on α2M clearance. Plasma elimination of α2M complex was also unaltered by pretreatment of mice with intravenous free cis-DDPt. 相似文献
2.
Sounak Gupta Andrew M. Hau Jordan R. Beach Jyoti Harwalker Elisabetta Mantuano Steven L. Gonias Thomas T. Egelhoff Donna E. Hansel 《PloS one》2013,8(11)
Bladder cancer is the fourth most common cause of cancer in males in the United States. Invasive behavior is a major determinant of prognosis. In this study, we identified mammalian target of rapamycin complex 2 (mTORC2) as a central regulator of bladder cancer cell migration and invasion. mTORC2 activity was assessed by the extent of phosphorylation of Ser473 in AKT and determined to be approximately 5-fold higher in specimens of invasive human bladder cancer as opposed to non-invasive human bladder cancer. The immortalized malignant bladder cell lines, UMUC-3, J82 and T24 demonstrated higher baseline mTORC2 activity relative to the benign bladder papilloma-derived cell line RT4 and the normal urothelial cell line HU1. The malignant bladder cancer cells also demonstrated increased migration in transwell and denudation assays, increased invasion of matrigel, and increased capacity to invade human bladder specimens. Gene silencing of rictor, a critical component of mTORC2, substantially inhibited bladder cancer cell migration and invasion. This was accompanied by a significant decrease in Rac1 activation and paxillin phosphorylation. These studies identify mTORC2 as a major target for neutralizing bladder cancer invasion. 相似文献
3.
JG Hansen W Gao J Dupuis GT O’Connor W Tang M Kowgier A Sood SA Gharib LJ Palmer M Fornage SR Heckbert BM Psaty SL Booth SUNLIGHT Consortium Patricia A Cassano 《Respiratory research》2015,16(1)
Background
Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.Methods
We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.Results
We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P = 0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P < 0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P = 0.09).Conclusions
Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0238-y) contains supplementary material, which is available to authorized users. 相似文献4.
Yan Lu Shulin/SL Li Shiguo/SG Zhu Yabin/YB Gong Jun/J Shi Ling/ L Xu 《Biological procedures online》2017,19(1):2
DNA/RNA methylation plays an important role in lung cancer initiation and progression. Liquid biopsy makes use of cells, nucleotides and proteins released from tumor cells into body fluids to help with cancer diagnosis and prognosis. Methylation of circulating tumor DNA (ctDNA) has gained increasing attention as biomarkers for lung cancer. Here we briefly introduce the biological basis and detection method of ctDNA methylation, and review various applications of methylated DNA in body fluids in lung cancer screening, diagnosis, prognosis, monitoring and treatment prediction. We also discuss the emerging role of RNA methylation as biomarkers for cancer. 相似文献
5.
Out of Africa and back again: nested cladistic analysis of human Y chromosome variation 总被引:18,自引:3,他引:15
Hammer MF; Karafet T; Rasanayagam A; Wood ET; Altheide TK; Jenkins T; Griffiths RC; Templeton AR; Zegura SL 《Molecular biology and evolution》1998,15(4):427-441
We surveyed nine diallelic polymorphic sites on the Y chromosomes of 1,544
individuals from Africa, Asia, Europe, Oceania, and the New World.
Phylogenetic analyses of these nine sites resulted in a tree for 10
distinct Y haplotypes with a coalescence time of approximately 150,000
years. The 10 haplotypes were unevenly distributed among human populations:
5 were restricted to a particular continent, 2 were shared between Africa
and Europe, 1 was present only in the Old World, and 2 were found in all
geographic regions surveyed. The ancestral haplotype was limited to African
populations. Random permutation procedures revealed statistically
significant patterns of geographical structuring of this paternal genetic
variation. The results of a nested cladistic analysis indicated that these
geographical associations arose through a combination of processes,
including restricted, recurrent gene flow (isolation by distance) and range
expansions. We inferred that one of the oldest events in the nested
cladistic analysis was a range expansion out of Africa which resulted in
the complete replacement of Y chromosomes throughout the Old World, a
finding consistent with many versions of the Out of Africa Replacement
Model. A second and more recent range expansion brought Asian Y chromosomes
back to Africa without replacing the indigenous African male gene pool.
Thus, the previously observed high levels of Y chromosomal genetic
diversity in Africa may be due in part to bidirectional population
movements. Finally, a comparison of our results with those from nested
cladistic analyses of human mtDNA and beta-globin data revealed different
patterns of inferences for males and females concerning the relative roles
of population history (range expansions) and population structure
(recurrent gene flow), thereby adding a new sex-specific component to
models of human evolution.
相似文献
6.
S W Hall L L Braud S L Gonias 《Biochemical and biophysical research communications》1989,164(3):1288-1294
Plasminogens were purified by affinity chromatography from bovine, ovine, porcine, canine, and rat plasma. The binding of each plasminogen to rat hepatocytes in primary culture and to rat C6 glioma cells was studied by radiodisplacement experiments. All of the plasminogens inhibited human 125I-[Glu1]plasminogen type 2 binding to specific cell surface receptors. The IC50 values were similar. These studies suggest conservation of the receptor recognition site in plasminogens across species lines. 相似文献
7.
Salmonella-induced aggregation of host endosomal compartments into tubules, termed lgp-tubules, requires sifA and ompR. Lgp-tubules result from Salmonella-directed alteration of the endocytic system and typify the unique intracellular locale where Salmonella replicate. A high-throughput method devised to screen 11 520 MudJ mutants for loss of lgp-tubule formation identified one auxotrophic and nine prototrophic mutants. Molecular characterization identified four new loci required to alter epithelial endocytic structure. Salmonella pathogenicity island 2 (SPI2) is the locus central to the phenotype. A subset of SPI2 effectors is essential: SpiC and SseFG are required, but not SseE. A subset of apparatus proteins is also implicated: SsaJ, L, M, V and P are required. SPI2 was implicated further, as SifA shows similarity with known SPI2 translocation targets, and OmpR regulates SPI2. Another locus lies within the smf-aroE intragenic region. Lgp-tubule formation also involves a locus on the virulence plasmid pSLT. The pSLT-encoded SpvR negatively regulates an unknown repressor of the phenotype located on pSLT. Finally, disruption of carB leads to multiple auxotrophy that prevents lgp-tubule formation. This study demonstrates that lgp-tubule formation is a virulence mechanism that underlies the selective disruption of host endocytic trafficking and is associated with the formation of a replication-permissive locale. 相似文献
8.
Gonias SL Carmichael A Mettenburg JM Roadcap DW Irvin WP Webb DJ 《The Journal of biological chemistry》2000,275(8):5826-5831
alpha(2)-Macroglobulin (alpha(2)M) functions as a proteinase inhibitor and as a carrier of diverse growth factors. In this study, we localized binding sites for platelet-derived growth factor-BB (PDGF-BB) and nerve growth factor-beta (NGF-beta) to a linear sequence in the 180-kDa human alpha(2)M subunit which includes amino acids 591-774. A glutathione S-transferase fusion protein containing amino acids 591-774 (FP3) bound PDGF-BB and NGF-beta in ligand blotting assays whereas five other fusion proteins, which collectively include amino acids 99-590 and 775-1451 did not. The K(D) values for PDGF-BB and NGF-beta binding to immobilized FP3 were 300 +/- 40 and 180 +/- 30 nM, respectively; these values were comparable with those determined using methylamine-modified alpha(2)M, suggesting that higher-order alpha(2)M structure is not necessary for PDGF-BB and NGF-beta binding. PDGF-BB and NGF-beta blocked the binding of transforming growth factor-beta1 (TGF-beta1) to FP3. Furthermore, murinoglobulin, which is the only known member of the alpha-macroglobulin family that does not bind TGF-beta, also failed to bind PDGF-BB and NGF-beta. These results support the hypothesis that either a single linear sequence in human alpha(2)M or overlapping sequences are responsible for the binding of TGF-beta, PDGF-BB, and NGF-beta, even though there is minimal sequence identity between these three growth factors. FP3 blocked the binding of PDGF-BB to a purified chimeric protein, in which the extracellular domain of the PDGF beta receptor was fused to the IgG(1) Fc domain, and to PDGF receptors on NIH 3T3 cells. Thus, FP3 may inhibit the activity of PDGF-BB. 相似文献
9.
Nancy L. Figler Dudley K. Strickland Margaretta Allietta Steven L. Gonias 《Journal of structural biology》1991,106(3)
α2-Macroglobulin (α2M) is a plasma proteinase inhibitor that binds up to 2 mole of proteinase per mole of inhibitor. Proteinase binding or reaction with small primary amines causes a major conformational change in α2M. As a result of this conformational change, a new epitope recognized by monoclonal antibody 7H11D6 is exposed. The association of α2M-proteinase or α2M-methylamine with α2M cellular receptors is prevented by 7H11D6. In this investigation, the binding of 7H11D6 to α2M was studied by electron microscopy. 7H11D6 bound to α2M-methylamine and α2M-trypsin but not to native α2M. The structure of α2M after conformational change resembled the letter “H.” 7H11D6 epitopes were identified near the apices of the four arms in the α2M “H” structure. 7H11D6 that was adducted to colloidal gold (7HAu) retained the specificity of the free antibody (binding to α2M-trypsin but not to native α2M). α2M conformational change intermediates prepared by sequential reaction with a protein crosslinker and trypsin also bound 7HAu. These results suggest that a complete α2M conformational change is not necessary for 7H11D6 epitope exposure and may not be required for receptor recognition. 7HAu was used to isolate a preparation consisting primarily of binary α2M-trypsin (1 mole trypsin per mole α2M instead of 2). Structures resembling the letter “H” were most common; however, each field showed some atypical molecules with arms that were compacted instead of thin and elongated. These incompletely transformed structures were similar to the α2M conformational intermediates described previously (S. L. Gonias and N. L. Figler (1989) J. Biol. Chem. 264, 9565–9570). We propose that lateral arm extension is a critical step in α2M conformational change. Failure of lateral arm extension is probably a common property of different α2M conformational intermediates. 相似文献
10.
Physical properties of human alpha 2-macroglobulin following reaction with methylamine and trypsin 总被引:14,自引:0,他引:14
Circular dichroism spectroscopy, sedimentation velocity and ultraviolet difference spectroscopy were used to compare alpha 2-macroglobulin, alpha 2-macroglobulin-trypsin complex and alpha 2-macroglobulin-methylamine complex. The circular dichroic spectrum of native alpha 2-macroglobulin is significantly changed in shape and magnitude following reaction with either trypsin or methylamine. The spectra of alpha 2-macroglobulin-trypsin and alpha 2-macroglobulin-methylamine are, however, indistinguishable. The ultraviolet difference spectrum between alpha 2-macroglobulin-methylamine and native alpha 2-macroglobulin displays a tyrosine blue shift consistent with the exposure of several tyrosine residues to solvent. The conformational change which occurs in alpha 2-macroglobulin during reaction with methylamine follows pseudo-first-order kinetics. T 1/2 was 10.5 min for the reaction with 200 mM methylamine at pH 8.0 and 45 min for the reaction with 50 mM methylamine, also at pH 8.0. Reaction of methylamine with alpha 2-macroglobulin results in loss of trypsin-binding activity which appears to be a direct consequence of the conformational change induced by methylamine. A sedimentation coefficient (S0(20),W) of 20.5 was determined for alpha 2-macroglobulin-methylamine compared to a value of 18.5 for unreacted alpha 2-macroglobulin. This increase in sedimentation velocity is attributed to a 10% decrease in alpha 2-macroglobulin Stokes radius. alpha 2-Macroglobulin-trypsin complex prepared by reaction of the protease at a 2-fold molar excess with the inhibitor was a S0(20),W of 20.3. Although this sedimentation coefficient does reflect compacting of the alpha 2-macroglobulin structure compared to native alpha 2-macroglobulin, it is not large enough to rule out significant protrusion of the proteases from pockets in the alpha 2-macroglobulin structure. 相似文献