全文获取类型
收费全文 | 53篇 |
免费 | 15篇 |
出版年
2021年 | 1篇 |
2018年 | 2篇 |
2017年 | 2篇 |
2016年 | 1篇 |
2015年 | 4篇 |
2014年 | 3篇 |
2013年 | 1篇 |
2012年 | 2篇 |
2011年 | 3篇 |
2010年 | 3篇 |
2009年 | 3篇 |
2008年 | 2篇 |
2007年 | 4篇 |
2005年 | 4篇 |
2004年 | 1篇 |
2003年 | 2篇 |
2002年 | 2篇 |
2000年 | 5篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1988年 | 4篇 |
1986年 | 2篇 |
1981年 | 1篇 |
1977年 | 1篇 |
排序方式: 共有68条查询结果,搜索用时 204 毫秒
31.
A mouse to human search for plasma proteome changes associated with pancreatic tumor development 总被引:1,自引:0,他引:1
Faca VM Song KS Wang H Zhang Q Krasnoselsky AL Newcomb LF Plentz RR Gurumurthy S Redston MS Pitteri SJ Pereira-Faca SR Ireton RC Katayama H Glukhova V Phanstiel D Brenner DE Anderson MA Misek D Scholler N Urban ND Barnett MJ Edelstein C Goodman GE Thornquist MD McIntosh MW DePinho RA Bardeesy N Hanash SM 《PLoS medicine》2008,5(6):e123
Background
The complexity and heterogeneity of the human plasma proteome have presented significant challenges in the identification of protein changes associated with tumor development. Refined genetically engineered mouse (GEM) models of human cancer have been shown to faithfully recapitulate the molecular, biological, and clinical features of human disease. Here, we sought to exploit the merits of a well-characterized GEM model of pancreatic cancer to determine whether proteomics technologies allow identification of protein changes associated with tumor development and whether such changes are relevant to human pancreatic cancer.Methods and Findings
Plasma was sampled from mice at early and advanced stages of tumor development and from matched controls. Using a proteomic approach based on extensive protein fractionation, we confidently identified 1,442 proteins that were distributed across seven orders of magnitude of abundance in plasma. Analysis of proteins chosen on the basis of increased levels in plasma from tumor-bearing mice and corroborating protein or RNA expression in tissue documented concordance in the blood from 30 newly diagnosed patients with pancreatic cancer relative to 30 control specimens. A panel of five proteins selected on the basis of their increased level at an early stage of tumor development in the mouse was tested in a blinded study in 26 humans from the CARET (Carotene and Retinol Efficacy Trial) cohort. The panel discriminated pancreatic cancer cases from matched controls in blood specimens obtained between 7 and 13 mo prior to the development of symptoms and clinical diagnosis of pancreatic cancer.Conclusions
Our findings indicate that GEM models of cancer, in combination with in-depth proteomic analysis, provide a useful strategy to identify candidate markers applicable to human cancer with potential utility for early detection. 相似文献32.
H?Bukulmez AL?Matthews CM?Sullivan C?Chen MJ?Kraay RC?Elston RW?Moskowitz VM?Goldberg ML?WarmanEmail author 《Arthritis research & therapy》2005,8(1):R25
In order to determine whether there is a genetic component to hip or knee joint failure due to idiopathic osteoarthritis (OA),
we invited patients (probands) undergoing hip or knee arthroplasty for management of idiopathic OA to provide detailed family
histories regarding the prevalence of idiopathic OA requiring joint replacement in their siblings. We also invited their spouses
to provide detailed family histories about their siblings to serve as a control group. In the probands, we confirmed the diagnosis
of idiopathic OA using American College of Rheumatology criteria. The cohorts included the siblings of 635 probands undergoing
total hip replacement, the siblings of 486 probands undergoing total knee replacement, and the siblings of 787 spouses. We
compared the prevalence of arthroplasty for idiopathic OA among the siblings of the probands with that among the siblings
of the spouses, and we used logistic regression to identify independent risk factors for hip and knee arthroplasty in the
siblings. Familial aggregation for hip arthroplasty, but not for knee arthroplasty, was observed after controlling for age
and sex, suggesting a genetic contribution to end-stage hip OA but not to end-stage knee OA. We conclude that attempts to
identify genes that predispose to idiopathic OA resulting in joint failure are more likely to be successful in patients with
hip OA than in those with knee OA. 相似文献
33.
34.
Studies of esterase 6 in Drosophila melanogaster. XVIII. Biochemical differences between the slow and fast allozymes 总被引:1,自引:0,他引:1
Most natural populations of Drosophila melanogaster are polymorphic for two
major electrophoretic variants at the esterase-6 locus. The frequency of
the EST 6F allozyme is greatest in populations in warmer latitudes, whereas
the EST 6S allozyme is predominant in colder latitudes. Latitudinal clines
in electromorph frequencies are found on three continents. Purified
preparations of the allozymes have been characterized for their pH optimum,
substrate specificity, organophosphate inhibition, alcohol activation,
thermal stability, and kinetic parameters. These and previous analyses of
the EST 6 allozymes reveal that the two variants have differences in their
physical and kinetic properties that may provide a basis for the selective
maintenance of the polymorphisms and an explanation of the clinal variation
observed in natural populations.
相似文献
35.
Suicide gene therapy of cancer is a method whereby cancerous tumors can be selectively eradicated while sparing damage to normal tissue. This is accomplished by delivering a gene, encoding an enzyme capable of specifically converting a nontoxic prodrug into a cytotoxin, to cancer cells followed by prodrug administration. The Escherichia coli gene, codA, encodes cytosine deaminase and is introduced into cancer cells followed by administration of the prodrug 5-fluorocytosine (5-FC). Cytosine deaminase converts 5-FC into cytotoxic 5-fluorouracil, which leads to tumor-cell eradication. One limitation of this enzyme/prodrug combination is that 5-FC is a poor substrate for bacterial cytosine deaminase. The crystal structure of bacterial cytosine deaminase (bCD) reveals that a loop structure in the active site pocket of wild-type bCD comprising residues 310-320 undergoes a conformational change upon cytosine binding, making several contacts to the pyrimidine ring. Alanine-scanning mutagenesis was used to investigate the structure-function relationship of amino acid residues within this region, especially with regard to substrate specificity. Using an E. coli genetic complementation system, seven active mutants were identified (F310A, G311A, H312A, D314A, V315A, F316A, and P318A). Further characterization of these mutants reveals that mutant F316A is 14-fold more efficient than the wild-type at deaminating cytosine to uracil. The mutant D314A enzyme demonstrates a dramatic decrease in cytosine activity (17-fold) as well as a slight increase in activity toward 5-FC (2-fold), indicating that mutant D314A prefers the prodrug over cytosine by almost 20-fold, suggesting that it may be a superior suicide gene. 相似文献
36.
Endogenous chloride channels of insect sf9 cells. Evidence for coordinated activity of small elementary channel units 总被引:1,自引:0,他引:1 下载免费PDF全文
EH Larsen SE Gabriei MJ Stutts J Fullton EM Price RC Boucher 《The Journal of general physiology》1996,107(6):695-714
The endogenous Cl- conductance of Spodoptera frugiperda (Sf9) cells was studied 20-35 h after plating out of either uninfected cells or cells infected by a baculovirus vector carrying the cloned beta-galactosidase gene (beta-Gal cells). With the cation Tris+ in the pipette and Na+ in the bath, the reversal potential of whole-cell currents was governed by the prevailing Cl- equilibrium potential and could be fitted by the Goldman-Hodgkin-Katz equation with similar permeabilities for uninfected and beta-Gal cells. In the frequency range 0.12 < f < 300 Hz, the power density spectrum of whole-cell Cl- currents could be fitted by three Lorentzians. Independent of membrane potential, >50% of the total variance of whole-cell current fluctuations was accounted for by the low frequency Lorentzian (fc = 0.40 +/- 0.03 Hz, n = 6). Single-Cl- channels showed complex gating kinetics with long lasting (seconds) openings interrupted by similar long closures. In the open state, channels exhibited fast burst-like closures. Since the patches normally contained more than a single channel, it was not possible to measure open and closed dwell-time distributions for comparing single-Cl- channel activity with the kinetic features of whole-cell currents. However, the power density spectrum of Cl- currents of cell-attached and excised outside-out patches contained both high and low frequency Lorentzian components, with the corner frequency of the slow component (fc = 0.40 +/- 0.02 Hz, n = 4) similar to that of whole-cell current fluctuations. Chloride channels exhibited multiple conductance states with similar Goldman-Hodgkin-Katz-type rectification. Single-channel permeabilities covered the range from approximately 0.6.10(-14) cm5/s to approximately 6.10(-14) cm3/s, corresponding to a limiting conductance (gamma 150/150) of approximately 3.5 pS and approximately 35 pS, respectively. All states reversed near the same membrane potential, and they exhibited similar halide ion selectivity, P1 > PCl approximately PBr. Accordingly, Cl- current amplitudes larger than current flow through the smallest channel unit resolved seem to result from simultaneous open/shut events of two or more channel units. 相似文献
37.
38.
The bacterial pathogen Listeria monocytogenes uses actin‐based motility to spread from infected human cells to surrounding healthy cells. Cell–cell spread involves the formation of thin extensions of the host plasma membrane (‘protrusions’) containing motile bacteria. In cultured enterocytes, the Listeria protein InlC promotes protrusion formation by binding and antagonizing the human scaffolding protein Tuba. Tuba is a known activator of the GTPase Cdc42. In this work, we demonstrate an important role for Cdc42 in controlling Listeria spread. Infection of the enterocyte cell line Caco‐2 BBE1 induced a decrease in the level of Cdc42‐GTP, indicating that Listeria downregulates this GTPase. Genetic data involving RNA interference indicated that bacterial impairment of Cdc42 may involve inhibition of Tuba. Experiments with dominant negative and constitutively activated alleles of Cdc42 demonstrated that the ability to inactivate Cdc42 is required for efficient protrusion formation by Listeria. Taken together, these findings indicate a novel mechanism of bacterial spread involving pathogen‐induced downregulation of host Cdc42. 相似文献
39.
Richa Singh Alexander J Mackay Anant RC Patel Davinder S Garcha Beverly S Kowlessar Simon E Brill Louise E Donnelly Peter J Barnes Gavin C Donaldson Jadwiga A Wedzicha 《Respiratory research》2014,15(1)
Background
There has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients. We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort.Methods
We prospectively collected sputum, serum and plasma samples for analysis of airway bacterial presence and load, and airway and systemic inflammation from 99 stable COPD patients between January 2011 and October 2012. Health status was measured with St George’s Respiratory Questionnaire and COPD Assessment Test.Results
Airway inflammation and plasma fibrinogen, but not C-reactive protein, were greater in samples with PPM detection (p < 0.001, p = 0.049 and p = 0.261, respectively). Increasing total bacterial load was associated with increasing airway (p < 0.01) but not systemic inflammation (p > 0.05). Samples with high total bacterial loads had significantly higher airway inflammation than both samples without PPM detection and those with lower loads. Haemophilus influenzae presence was associated with significantly higher levels of airway but not systemic inflammation for all given pathogen loads (p < 0.05), and was significantly greater than with other PPMs. No association was observed between inflammation and health status (p > 0.05).Conclusions
Airway and systemic inflammation, as measured by fibrinogen, is greater in stable COPD patients with PPMs detected using the culture-independent qPCR technique. The airway, but not systemic inflammatory response, appears to have a total pathogen-load threshold and appears attributable to Haemophilus influenzae. However, discordance between inflammation and health status was observed.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-014-0114-1) contains supplementary material, which is available to authorized users. 相似文献40.
A Jain M Sundriyal S Roshnibala R Kotoky PB Kanjilal HB Singh RC Sundriyal 《Journal of ethnobiology and ethnomedicine》2011,7(1):29