全文获取类型
收费全文 | 121篇 |
免费 | 13篇 |
专业分类
134篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2022年 | 2篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2017年 | 1篇 |
2016年 | 4篇 |
2015年 | 7篇 |
2014年 | 8篇 |
2013年 | 7篇 |
2012年 | 7篇 |
2011年 | 10篇 |
2010年 | 6篇 |
2009年 | 6篇 |
2008年 | 5篇 |
2007年 | 3篇 |
2006年 | 5篇 |
2005年 | 2篇 |
2004年 | 3篇 |
2003年 | 5篇 |
2002年 | 3篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1995年 | 1篇 |
1994年 | 4篇 |
1992年 | 1篇 |
1989年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1981年 | 2篇 |
1979年 | 3篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1974年 | 3篇 |
1973年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1967年 | 4篇 |
1966年 | 1篇 |
1965年 | 2篇 |
1964年 | 1篇 |
1963年 | 1篇 |
1959年 | 2篇 |
排序方式: 共有134条查询结果,搜索用时 15 毫秒
41.
Tim Vanuytsel Christophe Vanormelingen Hanne Vanheel Tatsuhiro Masaoka Shadea Salim Rasoel Joran Tóth Els Houben Kristin Verbeke Gert De Hertogh Pieter Vanden Berghe Jan Tack Ricard Farré 《PloS one》2014,9(10)
Background
Impaired intestinal barrier function, low-grade inflammation and altered neuronal control are reported in functional gastrointestinal disorders. However, the sequence of and causal relation between these events is unclear, necessitating a spontaneous animal model. The aim of this study was to describe the natural history of intestinal permeability, mucosal and neuromuscular inflammation and nitrergic motor neuron function during the lifetime of the BioBreeding (BB) rat.Methods
Normoglycemic BB-diabetes prone (DP) and control rats were sacrificed at different ages and jejunum was harvested to characterize intestinal permeability, inflammation and neuromuscular function.Results
Both structural and functional evidence of increased intestinal permeability was found in young BB-DP rats from the age of 50 days. In older animals, starting in the mucosa from 70 days and in half of the animals also in the muscularis propria from 110 days, an inflammatory reaction, characterized by an influx of polymorphonuclear cells and higher myeloperoxidase activity, was observed. Finally, in animals older than 110 days, coinciding with a myenteric ganglionitis, a loss of nitrergic neurons and motor function was demonstrated.Conclusion
In the BB-rat, mucosal inflammatory cell infiltration is preceded by intestinal barrier dysfunction and followed by myenteric ganglionitis and loss of nitrergic function. This sequence supports a primary role for impaired barrier function and provides an insightful model for the pathogenesis of functional gastrointestinal disorders. 相似文献42.
Mohamed Habbeddine Philippe Verbeke Sonia Karaz Pierre Bobé Colette Kanellopoulos-Langevin 《PloS one》2014,9(9)
Despite much interest in the mechanisms regulating fetal-maternal interactions, information on leukocyte populations and major cytokines present in uterus and placenta remains fragmentary. This report presents a detailed and quantitative study of leukocyte populations at the mouse fetal-maternal interface, including a comparison between pregnancies from syngeneic and allogeneic crosses. Our results provide evidence for drastic differences not only in the composition of leukocyte populations in the uterus during pregnancy, but also between uterine and placental tissues. Interestingly, we have observed a significant decrease in the number of myeloid Gr1+ cells including monocytes, and myeloid CD11c+ cells including DCs in placenta from an allogeneic pregnancy. In addition, we have compared the expression levels of a panel of cytokines in non-pregnant (NP) or pregnant mouse uterus, in placenta, or in their isolated resident leukocytes. Qualitative and quantitative differences have emerged between NP, pregnant uterus and placenta. Unexpectedly, IL-9 was the major cytokine in NP uterus, and was maintained at high levels during pregnancy both in uterus and placenta. Moreover, we have found that pregnancy is associated with an increase in uterine IL-1a and a significant decrease in uterine G-CSF and GM-CSF. Comparing allogeneic versus syngeneic pregnancy, less allogeneic placental pro-inflammatory cytokines CCL2 (MCP-1), CXCL10 (IP-10) and more IL1-α in whole uterus was reproducibly observed. To our knowledge, this is the first report showing a detailed overview of the leukocyte and cytokine repertoire in the uterus of virgin females and at the fetal-maternal interface, including a comparison between syngeneic and allogeneic pregnancy. This is also the first evidence for the presence of IL-9 in NP uterus and at the maternal-fetal interface, suggesting a major role in the regulation of local inflammatory or immune responses potentially detrimental to the conceptus. 相似文献
43.
Karen Windey Vicky De Preter Thierry Louat Frans Schuit Jean Herman Greet Vansant Kristin Verbeke 《PloS one》2012,7(12)
Objective
Protein fermentation results in production of metabolites such as ammonia, amines and indolic, phenolic and sulfur-containing compounds. In vitro studies suggest that these metabolites might be toxic. However, human and animal studies do not consistently support these findings. We modified protein fermentation in healthy subjects to assess the effects on colonic metabolism and parameters of gut health, and to identify metabolites associated with toxicity.Design
After a 2-week run-in period with normal protein intake (NP), 20 healthy subjects followed an isocaloric high protein (HP) and low protein (LP) diet for 2 weeks in a cross-over design. Protein fermentation was estimated from urinary p-cresol excretion. Fecal metabolite profiles were analyzed using GC-MS and compared using cluster analysis. DGGE was used to analyze microbiota composition. Fecal water genotoxicity and cytotoxicity were determined using the Comet assay and the WST-1-assay, respectively, and were related to the metabolite profiles.Results
Dietary protein intake was significantly higher during the HP diet compared to the NP and LP diet. Urinary p-cresol excretion correlated positively with protein intake. Fecal water cytotoxicity correlated negatively with protein fermentation, while fecal water genotoxicity was not correlated with protein fermentation. Heptanal, 3-methyl-2-butanone, dimethyl disulfide and 2-propenyl ester of acetic acid are associated with genotoxicity and indole, 1-octanol, heptanal, 2,4-dithiapentane, allyl-isothiocyanate, 1-methyl-4-(1-methylethenyl)-benzene, propionic acid, octanoic acid, nonanoic acid and decanoic acid with cytotoxicity.Conclusion
This study does not support a role of protein fermentation in gut toxicity. The identified metabolites can provide new insight into colonic health.Trial Registration
ClinicalTrial.gov NCT01280513相似文献44.
Sebastian Dempe Muriel Lavie Sofie Struyf Rauf Bhat Hannelien Verbeke Stephanie Paschek Nele Berghmans Renate Geibig Jean Rommelaere Jo Van Damme Christiane Dinsart 《Cancer immunology, immunotherapy : CII》2012,61(11):2113-2123
Pancreatic ductal adenocarcinoma (PDAC) represents the fourth leading cause of cancer-related death in western countries. The patients are often diagnosed in advanced metastatic stages, and the prognosis remains extremely poor with an overall 5-year survival rate less than 5?%. Currently, novel therapeutic strategies are being pursued to combat PDAC, including oncolytic viruses, either in their natural forms or armed with immunostimulatory molecules. Natural killer cells are critical players against tumours and infected cells. Recently, we showed that IL-2-activated human NK cells displayed killing activity against PDAC cells, which could further be enhanced through the infection of PDAC cells with the rodent parvovirus H-1PV. In this study, the therapeutic efficacy of parvovirus-mediated delivery of three distinct cyto/chemokines (Il-2, MCP-3/CCL7 and IP-10/CXCL10) was evaluated in xenograft models of human PDAC. We show here that activated NK and monocytic cells were found to be recruited by PDAC tumours upon infection with parvoviruses armed with IL-2 or the chemokine MCP-3/CCL7, resulting in a strong anti-tumour response. 相似文献
45.
Summary . In the analyses of incomplete longitudinal clinical trial data, there has been a shift, away from simple methods that are valid only if the data are missing completely at random, to more principled ignorable analyses, which are valid under the less restrictive missing at random assumption. The availability of the necessary standard statistical software nowadays allows for such analyses in practice. While the possibility of data missing not at random (MNAR) cannot be ruled out, it is argued that analyses valid under MNAR are not well suited for the primary analysis in clinical trials. Rather than either forgetting about or blindly shifting to an MNAR framework, the optimal place for MNAR analyses is within a sensitivity-analysis context. One such route for sensitivity analysis is to consider, next to selection models, pattern-mixture models or shared-parameter models. The latter can also be extended to a latent-class mixture model, the approach taken in this article. The performance of the so-obtained flexible model is assessed through simulations and the model is applied to data from a depression trial. 相似文献
46.
Patients who have undergone renal transplantation are monitored longitudinally at irregular time intervals over 10 years or more. This yields a set of biochemical and physiological markers containing valuable information to anticipate a failure of the graft. A general linear, generalized linear, or nonlinear mixed model is used to describe the longitudinal profile of each marker. To account for the correlation between markers, the univariate mixed models are combined into a multivariate mixed model (MMM) by specifying a joint distribution for the random effects. Due to the high number of markers, a pairwise modeling strategy, where all possible pairs of bivariate mixed models are fitted, is used to obtain parameter estimates for the MMM. These estimates are used in a Bayes rule to obtain, at each point in time, the prognosis for long-term success of the transplant. It is shown that allowing the markers to be correlated can improve this prognosis. 相似文献
47.
Chris van der Schoot Margaret A. Dietrich Marc Storms Judith A. Verbeke William J. Lucas 《Planta》1995,195(3):450-455
In the evolutionarily advanced angiosperm flower, postgenital fusion is often involved in the formation of the female reproductive organ, the gynoecium. In the present study, we report on the early establishment of a cytoplasmic cell-to-cell communication pathway between the two fusing carpel primordia in Catharanthus roseus L. (periwinkle). Upon carpel contact, diffusible factors move between the two carpels to initiate the rapid redifferentiation of epidermal cells into parenchymatous cells, resulting in carpel fusion. Microinjection of the lipid-impermeable molecule, Lucifer Yellow CH (LYCH), into cells on either side of the epidermal fusion plane revealed that cytoplasmic continuity was established very early in this redifferentiation process. Electron-microscopic analysis confirmed that this inter-carpel cytoplasmic coupling was established by the formation of plasmodesmata produced between the contacting epidermal cells. The evolution of and role for this inter-carpel communication pathway is discussed in terms of the coordinate development of the gynoecium and its overall effect on reproductive fitness. 相似文献
48.
Eddy Roets Roger Verbeke Anne-Marie Massart-Le?n Georges Peeters 《The Biochemical journal》1974,144(3):435-446
1. A lactating-sheep mammary gland was perfused for 12h in the presence of l-[2-(14)C]-citrulline and received adequate quantities of glucose, acetate and amino acids. Two lactating-goat udders were similarly perfused in the presence of either l-[carbamoyl-(14)C,-2-(14)C]citrulline or l-[carbamoyl-(14)C,1-(14)C]citrulline and l-[4-(3)H]arginine. 2. In these experiments, [(14)C]citrulline was substantially oxidized to CO(2) and converted into arginine and proline of casein. 3. The specific radioactivities of arginine, ornithine and proline of the plasma increased after passage through the udders, demonstrating that [(14)C]citrulline is metabolized by the mammary gland. 4. The presence of two unknown radioactive metabolites of [(14)C]citrulline was detected in the perfusate. These substances were not found after incubation in vitro of oxygenated blood in the presence of the radioactive precursor. 5. From these experiments, it is concluded that citrulline is metabolized in mammary tissue by way of arginine to urea, ornithine and proline. 相似文献
49.
F H Van Cauwelaert M N Verbeke 《Biochemical and biophysical research communications》1979,89(2):414-419
Spores of Phycomyces were scanned in a Differential Scanning Calorimeter. The spectrum obtained was clearly influenced by previous activation of spores by heat or by acetate.When spores were allowed to return to dormancy the original spectrum of dormant spores was restored. The high temperature at which the difference in the spectrum between activated and dormant spores was found points to a protein denaturation. It is suggested therefore that the activation of spores is obtained through a conformational change of a protein. 相似文献
50.
The use of score tests for inference on variance components 总被引:4,自引:0,他引:4
Whenever inference for variance components is required, the choice between one-sided and two-sided tests is crucial. This choice is usually driven by whether or not negative variance components are permitted. For two-sided tests, classical inferential procedures can be followed, based on likelihood ratios, score statistics, or Wald statistics. For one-sided tests, however, one-sided test statistics need to be developed, and their null distribution derived. While this has received considerable attention in the context of the likelihood ratio test, there appears to be much confusion about the related problem for the score test. The aim of this paper is to illustrate that classical (two-sided) score test statistics, frequently advocated in practice, cannot be used in this context, but that well-chosen one-sided counterparts could be used instead. The relation with likelihood ratio tests will be established, and all results are illustrated in an analysis of continuous longitudinal data using linear mixed models. 相似文献