全文获取类型
收费全文 | 97篇 |
免费 | 10篇 |
出版年
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 6篇 |
2015年 | 1篇 |
2014年 | 2篇 |
2013年 | 6篇 |
2012年 | 6篇 |
2011年 | 4篇 |
2010年 | 4篇 |
2009年 | 2篇 |
2008年 | 3篇 |
2007年 | 3篇 |
2006年 | 7篇 |
2005年 | 5篇 |
2004年 | 4篇 |
2003年 | 3篇 |
2002年 | 3篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1994年 | 1篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 6篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1979年 | 4篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1973年 | 4篇 |
1972年 | 2篇 |
1971年 | 2篇 |
排序方式: 共有107条查询结果,搜索用时 68 毫秒
1.
Reinhard Piechocki Dagmar Kupper Ariel Quiñones Renate Langhammer 《Molecular & general genetics : MGG》1986,202(1):162-168
Summary The dnaQ (mutD) gene product which encodes the -subunit of the DNA polymerase III holoenzyme has a central role in controlling the fidelity of DNA replication because both mutD5 and dnaQ49 mutations severely decrease the 3–5 exonucleolytic editing capacity.It is shown in this paper that more than 95% of all anaQ49-induced base pair substitutions are transversions of the types G:C-T:A and A:T-T:A. Not only is this unusual mutational specificity precisely that observed recently for a number of potent carcinogens such as benzo(a) pyrene diolepoxide (BPDE) and aflatoxin B1 (AFB1), which are dependent on the SOS system to mutagenize bacteria, but it is also seen for the constitutively expressed SOS mutator activity in E. coli tif-1 strains as well as for the SOS mutator activity mediated gap filling of apurinic sites. Because the G:C-T:A and A:T-T:A transversions can either result from the insertion of an adenine across from apurinic sites or arise due to the incorporation of syn-adenine opposite a purine base, we postulate that the DNA polymerase III holoenzyme also has a reduced discrimination ability in a dnaQ49 background.The introduction of a lexA (Ind-) allele, which prevents the expression of SOS functions, led to a significant reduction in the dnaQ49-caused mutator effect.Both, the mutational specificity observed and the partial lexA
+ dependence of the mutator effect provoke a reanalysis of the hypothesis that the DNA polymerase III holoenzyme can be converted into the postulated but until now unidentified SOS polymerase. 相似文献
2.
A rhesus monkey (Macaca mulatta), accidentally exposed to vapors of methyl methacrylate for 22 hours was found in a comatose condition. Attempts to revive the animal were unsuccessful. Necropsy revealed a diffusely mottled liver, pulmonary edema, and atelectasis. The thoracic cavities each contained 30 ml of clear yellow fluid. Histopathologic review of the tissues showed central lobular liver necrosis, pulmonary edema, pulmonary emphysema, and atelectasis. Analysis of a blood sample obtained from the monkey 1.5 hours prior to death showed a normal hemogram, but elevated values for serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, lactate dehydrogenase, phosphohexose isomerase, blood urea nitrogen, and serum sodium. The pathologic findings, laboratory results, and clinical history suggested a diagnosis of methyl methacrylate poisoning. 相似文献
3.
Jonathan Shoag Rizwan Haq Mingfeng Zhang Laura Liu Glenn C. Rowe Aihua Jiang Nicole Koulisis Caitlin Farrel Christopher I. Amos Qingyi Wei Jeffrey E. Lee Jiangwen Zhang Thomas S. Kupper Abrar A. Qureshi Rutao Cui Jiali Han David E. Fisher Zoltan Arany 《Molecular cell》2013,49(1):145-157
Highlights? PGC-1 induces pigment formation in melanocytes ? PGC-1s activate expression of MITF ? α-MSH induces PGC-1s, which are required for induction of melanogenic genes ? eQTLs in human PGC-1β are associated with tanning ability and melanoma protection 相似文献
4.
5.
Proteomics analysis of cytokine-induced dysfunction and death in insulin-producing INS-1E cells: new insights into the pathways involved 总被引:1,自引:0,他引:1
D'Hertog W Overbergh L Lage K Ferreira GB Maris M Gysemans C Flamez D Cardozo AK Van den Bergh G Schoofs L Arckens L Moreau Y Hansen DA Eizirik DL Waelkens E Mathieu C 《Molecular & cellular proteomics : MCP》2007,6(12):2180-2199
Cytokines released by islet-infiltrating immune cells play a crucial role in beta-cell dysfunction and apoptotic cell death in the pathogenesis of type 1 diabetes and after islet transplantation. RNA studies revealed complex pathways of genes being activated or suppressed during this beta-cell attack. The aim of the present study was to analyze protein changes in insulin-producing INS-1E cells exposed to inflammatory cytokines in vitro using two-dimensional DIGE. Within two different pH ranges we observed 2214 +/- 164 (pH 4-7) and 1641 +/- 73 (pH 6-9) spots. Analysis at three different time points (1, 4, and 24 h of cytokine exposure) revealed that the major changes were taking place only after 24 h. At this time point 158 proteins were altered in expression (4.1%, n = 4, p < or = 0.01) by a combination of interleukin-1beta and interferon-gamma, whereas only 42 and 23 proteins were altered by either of the cytokines alone, giving rise to 199 distinct differentially expressed spots. Identification of 141 of these by MALDI-TOF/TOF revealed proteins playing a role in insulin secretion, cytoskeleton organization, and protein and RNA metabolism as well as proteins associated with endoplasmic reticulum and oxidative stress/defense. We investigated the interactions of these proteins and discovered a significant interaction network (p < 1.27e-05) containing 42 of the identified proteins. This network analysis suggests that proteins of different pathways act coordinately in a beta-cell dysfunction/apoptotic beta-cell death interactome. In addition the data suggest a central role for chaperones and proteins playing a role in RNA metabolism. As many of these identified proteins are regulated at the protein level or undergo post-translational modifications, a proteomics approach, as performed in this study, is required to provide adequate insight into the mechanisms leading to beta-cell dysfunction and apoptosis. The present findings may open new avenues for the understanding and prevention of beta-cell loss in type 1 diabetes. 相似文献
6.
Information from detectable exposure measurements randomly sampled from a left-truncated log-normal distribution may be used to evaluate the distribution of nondetectable values that fall below an analytic limit of detection. If the proportion of nondetects is larger than expected under log normality, alternative models to account for these unobserved data should be considered. We discuss one such model that incorporates a mixture of true zero exposures and a log-normal distribution with possible left censoring, previously considered in a different context by Moulton and Halsey (1995, Biometrics 51, 1570-1578). A particular relationship is demonstrated between maximum likelihood parameter estimates based on this mixture model and those assuming either left-truncated or left-censored data. These results emphasize the need for caution when choosing a model to fit data involving nondetectable values. A one-sided likelihood ratio test for comparing mean exposure under the mixture model to an occupational exposure limit is then developed and evaluated via simulations. An example demonstrates the potential impact of specifying an incorrect model for the nondetectable values. 相似文献
7.
Banning A Schnurr K Böl GF Kupper D Müller-Schmehl K Viita H Ylä-Herttuala S Brigelius-Flohé R 《Free radical biology & medicine》2004,36(2):135-144
Cytokines or hydroperoxides upregulate cell adhesion molecules (CAM) in early stages of atherosclerosis. VCAM-1 expression was therefore investigated in rabbit aortic smooth muscle cells (SMC) stably transfected either with phospholipid hydroperoxide glutathione peroxidase (PHGPx; SMCPHGPx) as a hydroperoxide-reducing enzyme or with 15-lipoxygenase (15-LOX; SMCLOX) as a hydroperoxide-producing enzyme. Transfected cells showed up to 3-fold enhanced PHGPx and a marked LOX activity, respectively, that was absent in controls. Intracellular hydroperoxides were 6-fold higher in SMCLOX than in SMC or SMCPHGPx. Intracellular protein thiols were decreased by 50 and 90% in SMCPHGPx and SMCLOX, respectively. Glutathione mixed disulfides were tentatively increased from SMC via SMCPHGPx to SMCLOX, accordingly. Thiol reduction with tris(2-carboxyethyl)phosphine completely restored protein thiols in SMCPHGPx, whereas in SMCLOX only 60% of control values were recovered. Basal VCAM-1 mRNA levels were decreased by 50% in SMCPHGPx and 75% in SMCLOX. VCAM-1-inducibility was abrogated in SMCLOX but not in SMCPHGPx. Accordingly, NFkappaB-driven reporter gene activation by IL-1 was unaffected in SMCPHGPx but abolished in SMCLOX. The data confirm that PHGPx overexpression dampens CAM expression either by lowering stimulatory hydroperoxides or by using hydroperoxides for protein modification. But hydroperoxides, when constitutively overproduced as in SMCLOX, inhibit CAM expression and render cells refractory to IL-1 stimulation likely due to oxidation of protein thiols of the signaling system. 相似文献
8.
9.
Autogenic training: a meta-analysis of clinical outcome studies 总被引:3,自引:0,他引:3
Autogenic training (AT) is a self-relaxation procedure by which a psychophysiological determined relaxation response is elicited. A meta-analysis was performed to evaluate the clinical effectiveness of AT. Seventy-three controlled outcome studies were found (published 1952–99). Sixty studies (35 randomized controlled trials [RCT]) qualified for inclusion in the meta-analysis. Medium-to-large effect sizes (ES) occurred for pre–post comparisons of disease-specific AT-effects, with the RCTs showing larger ES. When AT was compared to real control conditions, medium ES were found. Comparisons of AT versus other psychological treatment mostly resulted in no effects or small negative ES. This pattern of results was stable at follow-up. Unspecific AT-effects (i.e., effects on mood, cognitive performance, quality of life, and physiological variables) tended to be even larger than main effects. Separate meta-analyses for different disorders revealed a significant reduction of the heterogeneity of ES. Positive effects (medium range) of AT and of AT versus control in the meta-analysis of at least 3 studies were found for tension headache/migraine, mild-to-moderate essential hypertension, coronary heart disease, asthma bronchiale, somatoform pain disorder (unspecified type), Raynaud's disease, anxiety disorders, mild-to-moderate depression/dysthymia, and functional sleep disorders. 相似文献
10.
Yamanaka K Tanaka M Tsutsui H Kupper TS Asahi K Okamura H Nakanishi K Suzuki M Kayagaki N Black RA Miller DK Nakashima K Shimizu M Mizutani H 《Journal of immunology (Baltimore, Md. : 1950)》2000,165(2):997-1003
To study the pathophysiological roles of overexpressed caspase-1 (CASP1), originally designated as IL-1 beta-converting enzyme, we generated transgenic mice in which human CASP1 is overexpressed in their keratinocytes. The transgenic mice spontaneously developed recalcitrant dermatitis and skin ulcers, characterized by the presence of massive keratinocyte apoptosis. The skin of the mice contained the active form of human CASP1 and expressed mRNA for caspase-activated DNase, an effector endonuclease responsible for DNA fragmentation. Their skin and sera showed elevated levels of mature IL-18 and IL-1 beta, but not of IFN-gamma. The plasma from these animals induced IFN-gamma production by IL-18-responsive NK cells. Administration of heat-killed Propionibacterium acnes, a potent in vivo type 1 cell inducer, caused IFN-gamma-mediated lethal liver injury in the transgenic mice, which was completely inhibited by treatment with neutralizing anti-IL-18 Ab. These results indicated that in vivo overexpression of CASP1 caused spontaneous apoptotic tissue injury and rendered mice highly susceptible to exogenous type 1 cell-inducing condition in collaboration with endogenously accumulated proinflammatory cytokines. 相似文献