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排序方式: 共有93条查询结果,搜索用时 312 毫秒
1.
A simulation approach for power calculation in large cohort studies based on multistate models
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Bastian Jenny Jan Beyersmann Martin Schumacher 《Biometrical journal. Biometrische Zeitschrift》2018,60(4):671-686
Realistic power calculations for large cohort studies and nested case control studies are essential for successfully answering important and complex research questions in epidemiology and clinical medicine. For this, we provide a methodical framework for general realistic power calculations via simulations that we put into practice by means of an R‐based template. We consider staggered recruitment and individual hazard rates, competing risks, interaction effects, and the misclassification of covariates. The study cohort is assembled with respect to given age‐, gender‐, and community distributions. Nested case‐control analyses with a varying number of controls enable comparisons of power with a full cohort analysis. Time‐to‐event generation under competing risks, including delayed study‐entry times, is realized on the basis of a six‐state Markov model. Incidence rates, prevalence of risk factors and prefixed hazard ratios allow for the assignment of age‐dependent transition rates given in the form of Cox models. These provide the basis for a central simulation‐algorithm, which is used for the generation of sample paths of the underlying time‐inhomogeneous Markov processes. With the inclusion of frailty terms into the Cox models the Markov property is specifically biased. An “individual Markov process given frailty” creates some unobserved heterogeneity between individuals. Different left‐truncation‐ and right‐censoring patterns call for the use of Cox models for data analysis. p‐values are recorded over repeated simulation runs to allow for the desired power calculations. For illustration, we consider scenarios with a “testing” character as well as realistic scenarios. This enables the validation of a correct implementation of theoretical concepts and concrete sample size recommendations against an actual epidemiological background, here given with possible substudy designs within the German National Cohort. 相似文献
2.
A two-step purification procedure for 5-aminolevulinic acid dehydratase (EC 4.2.1.24) from human red blood cells has been developed. It involves one ion exchange and one gel filtration step. The purification is about 1000-fold, and the yield is more than 85%. With the purified enzyme a direct spectrophotometric assay of product formation without subsequent reaction with Ehrlich's reagent is described. 相似文献
3.
Small angle X-ray scattering study on bovine porphobilinogen synthase (5-aminolaevulinate dehydratase) 总被引:1,自引:0,他引:1
The quaternary structure of the native (zinc) porphobilinogen synthase (5-amino-laevulinate dehydratase) from bovine liver and its lead-substituted derivative is studied in solution by small angle X-ray scattering. In spite of the profound inhibitory effect of lead ions in the enzyme they do not produce a change in the quaternary structure detectable by small angle X-ray scattering. The most important molecular parameters of the native enzyme were found to be: radius of gyration Rg = 4.04 +/- 0.04 nm and maximum dimension Dmax = 12.0 +/- 0.5 nm. The corresponding values for the lead derivative are: Rg = 4.26 +/- 0.1 nm and Dmax = 12.5 +/- 0.5 nm. The quaternary structure of the enzyme in solution is described by a model, which fits the experimental scattering and distance distribution function. 相似文献
4.
Temperature-sensitive initiation of DNA replication in a mutant of Escherichia coli K12 总被引:16,自引:0,他引:16
Detmar Beyersmann Marianne Schlicht Heinz Schuster 《Molecular & general genetics : MGG》1971,111(2):145-158
Summary A mutant of E. coli K12 appears to be temperature-sensitive in the process of initiation of DNA replication. After a temperature shift from 33 to 42°C, the amount of residual DNA synthesis (Fig. 1) and the number of residual cell divisions (Figs. 2,4) indicate that rounds of DNA replication in process are completed, but new rounds cannot be initiated. Following the alignment of chromosomal DNA by amino acid starvation at 33° C no residual DNA synthesis at 42°C takes place (Fig. 5). When the temperature is lowered to 33°C after a period of inhibition at 42°C, the following observations are made: 1. DNA replication resumes and proceeds synchroneously, (Figs. 7, 8a), 2. cells start to divide again only after a lag period of about 1 hour 3. a temporary increase in cell volume is correlated with the frequency of initiation of DNA synthesis (Fig. 8a, b). In a lysogenic mutant strain prophage is inducible; with all bacteriophages tested, replication of phage DNA is not inhibited at 42°C. 相似文献
5.
The DNA cleavage induced by a chromium(V) complex and by chromate and glutathione is mediated by activated oxygen species 总被引:2,自引:0,他引:2
The number of strand breaks induced by the combination of chromate and glutathione (GSH) in PM2 DNA was effectively reduced upon addition of the hydroxyl radical scavengers dimethyl sulphoxide (DMSO), formate and benzoate. Administration of catalase also led to a depression of DNA degradation whereas superoxide dismutase (SOD) had very little influence. Essentially the same results were obtained in experiments employing a chromium(V) complex Na4(GSH)4Cr.8H20, which is an intermediate chromium species isolated from the reduction of chromate by glutathione. DNA cleavage was dependent on the presence of iron (FeCl3). When compared with the number of breaks produced by FeCl3 and GSH alone, chromate stimulated the generation of single-strand breaks. These findings suggest that hydroxyl radicals are one ultimate DNA cleaving agent in both reactions. A reaction scheme for the production of hydroxyl radicals is proposed. 相似文献
6.
Yahata Y Shirakata Y Tokumaru S Yamasaki K Sayama K Hanakawa Y Detmar M Hashimoto K 《The Journal of biological chemistry》2003,278(41):40026-40031
7.
An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype 总被引:55,自引:0,他引:55
Wigle JT Harvey N Detmar M Lagutina I Grosveld G Gunn MD Jackson DG Oliver G 《The EMBO journal》2002,21(7):1505-1513
The process of angiogenesis has been well documented, but little is known about the biology of lymphatic endothelial cells and the molecular mechanisms controlling lymphangiogenesis. The homeobox gene Prox1 is expressed in a subpopulation of endothelial cells that, after budding from veins, gives rise to the mammalian lymphatic system. In Prox1(-)(/-) embryos, this budding becomes arrested at around embryonic day (E)11.5, resulting in embryos without lymphatic vasculature. Unlike the endothelial cells that bud off in E11.5 wild-type embryos, those of Prox1-null embryos did not co-express any lymphatic markers such as VEGFR-3, LYVE-1 or SLC. Instead, the mutant cells appeared to have a blood vascular phenotype, as determined by their expression of laminin and CD34. These results suggest that Prox1 activity is required for both maintenance of the budding of the venous endothelial cells and differentiation toward the lymphatic phenotype. On the basis of our findings, we propose that a blood vascular phenotype is the default fate of budding embryonic venous endothelial cells; upon expression of Prox1, these budding cells adopt a lymphatic vasculature phenotype. 相似文献
8.
9.
Zinc ions are essential, but at elevated concentrations, they also have toxic effects on mammalian cells. Zinc plays a crucial
role in cell proliferation and differentiation and it even protects cells against apoptosis caused by various reagents. On
the other hand, zinc at high concentrations causes cell death that was characterized as apoptotic by internucleosomal DNA
fragmentation, formation of apoptotic bodies, and breakdown of the mitochondrial membrane potential. In the present work,
a clone of rat C6 glioma cells that was resistant to toxic effects of ZnCl2 up to 250 μM was employed to study the effect of the ionophore A23187 on zinc-induced apoptosis. Neither 150 μM Zn2+ nor 100 nM A23187 alone caused apoptosis as measured by internucleosomal DNA fragmentation. However, combined exposure of C6 cells to
100 nM A23187 and 150 μM Zn2+ for 48 h was effective in inducing apoptosis. Because the so-called calcium ionophore A23187 is not specific for Ca2+ ions but also transports Zn2+ with high selectivity over Ca2+, we investigated whether this substance promoted the uptake of Zn2+ ions into C6 cells. Employing the zinc-specific fluorescence probe Zinquin, we observed that the very low concentration of
1.9 nM A23187 significantly and rapidly raised the intracellular mobile Zn2+ content. Analysis by atomic absorption spectroscopy revealed that incubation with 1.9 nM A23187 caused a doubling of the total intracellular zinc level within 60 min. We conclude that the apoptosis evoked by the
combined action of Zn2+ and A23187 was the result of enhanced Zn2+ influx evoked by the ionophore, resulting in higher intracellular zinc levels. 相似文献
10.
T1alpha/podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema 总被引:25,自引:0,他引:25
Schacht V Ramirez MI Hong YK Hirakawa S Feng D Harvey N Williams M Dvorak AM Dvorak HF Oliver G Detmar M 《The EMBO journal》2003,22(14):3546-3556
Within the vascular system, the mucin-type transmembrane glycoprotein T1alpha/podoplanin is predominantly expressed by lymphatic endothelium, and recent studies have shown that it is regulated by the lymphatic-specific homeobox gene Prox1. In this study, we examined the role of T1alpha/podoplanin in vascular development and the effects of gene disruption in mice. T1alpha/podoplanin is first expressed at around E11.0 in Prox1-positive lymphatic progenitor cells, with predominant localization in the luminal plasma membrane of lymphatic endothelial cells during later development. T1alpha/podoplanin(-/-) mice die at birth due to respiratory failure and have defects in lymphatic, but not blood vessel pattern formation. These defects are associated with diminished lymphatic transport, congenital lymphedema and dilation of lymphatic vessels. T1alpha/podoplanin is also expressed in the basal epidermis of newborn wild-type mice, but gene disruption did not alter epidermal differentiation. Studies in cultured endothelial cells indicate that T1alpha/podoplanin promotes cell adhesion, migration and tube formation, whereas small interfering RNA-mediated inhibition of T1alpha/podoplanin expression decreased lymphatic endothelial cell adhesion. These data identify T1alpha/podoplanin as a novel critical player that regulates different key aspects of lymphatic vasculature formation. 相似文献