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51.
Bjorn?WH?van Heumen Hennie?MJ?Roelofs René?HM?te Morsche Fokko?M?Nagengast Wilbert?HM?PetersEmail author 《Orphanet journal of rare diseases》2013,8(1):181
Background
Familial adenomatous polyposis (FAP) is a disease characterized by the development of hundreds to thousands of adenomatous polyps in the colorectum early in life. Virtually all patients with FAP will develop colorectal cancer before the age of 40 to 50 years, unless prophylactic colectomy is performed, which significantly improves their prognosis. The mortality pattern has changed and duodenal cancer now is one of the main cancer-related causes of death in these patients. Practically all patients with FAP develop premalignant duodenal adenomas, which may develop to duodenal cancer in approximately 3-7% of patients. Duodenal cancer in patients with FAP has a poor prognosis. The clinical challenge is to identify patients at high-risk for duodenal carcinoma. Chemoprevention would be desirable to avoid duodenectomy. The main goal of this study is to identify risk markers in normal duodenal mucosa of patients with FAP, that could help identify patients at increased risk for malignant transformation.Methods
Messenger RNA (mRNA) levels of glutathione S-transferase A1 (GSTA1), glutathione S-transferase P1 (GSTP1), KIAA1199, E-cadherin, peroxisome proliferative activated receptor δ (PPARδ), caspase-3, cyclin D1, β-catenin, and cyclooxygenase-2 (COX-2) were measured in duodenal mucosa, using the QuantiGene 2.0 Plex assay. Levels in normal appearing mucosa of patients with FAP (n?=?37) were compared with levels in non-FAP patient controls (n?=?16). In addition, levels before and after treatment with either celecoxib & ursodeoxycholic acid (UDCA, n?=?14) or celecoxib & placebo (n?=?13) were evaluated in patients with FAP.Results
mRNA levels of glutathione S-transferase A1 (28.16% vs. 38.24%, p?=?0.008) and caspase-3 (3.30% vs. 5.31%, p?=?0.001) were significantly lower in patients with FAP vs. non-FAP patient controls, respectively. COX-2 mRNA levels in normal duodenal mucosa of patients with FAP were found to be unexpectedly low. None of the potential risk markers was influenced by celecoxib or celecoxib & UDCA.Conclusions
Protection against toxins and carcinogens (GSTA1) and apoptosis (caspase-3) is low in patients with FAP, which could contribute to increased susceptibility for malignant transformation of duodenal mucosa.Trial registration
http://ClinicalTrials.gov number NCT0080874352.
We present a simple Monte Carlo method for estimating the age of the most
recent common ancestor (MRCA) of a sample of DNA sequences. We show that
Templeton's (1993) estimator of the age of the MRCA based on the maximum
number of nucleotide differences between two sequences in a sample is
inaccurate, and we demonstrate the new method by reanalyzing a sample of
DNA sequences from human Y chromosomes and a sample of human Alu sequences.
相似文献
53.
Purification and characterization of human interleukin-1 beta expressed in recombinant Escherichia coli 总被引:14,自引:0,他引:14
P Wingfield M Payton J Tavernier M Barnes A Shaw K Rose M G Simona S Demczuk K Williamson J M Dayer 《European journal of biochemistry》1986,160(3):491-497
The high-level expression of human interleukin-1 beta in Escherichia coli is described. The protein contributes about 12% of the total cell protein and is associated with the soluble cytoplasmic fraction of the cell. A method for the purification of the protein is given which is based on anion- and cation-exchange chromatographies. The isolated protein, shown to be homogeneous by several analytical methods, has been characterized by amino acid analysis, N- and C-terminal sequence analysis and analytical centrifugation. The protein is biologically active as demonstrated by two different in vitro assays, namely, the mononuclear cell factor (IL-1/MCF) assay and lymphocyte activating factor (IL-1/LAF) assay. The specific activities determined with the IL-1/MCF and IL-1/LAF assays, are 2 X 10(7) and 4 X 10(7) units mg-1, respectively. 相似文献
54.
Differential effects of in vitro mycoplasma infection on interleukin-1 alpha and beta mRNA expression in U937 and A431 cells 总被引:3,自引:0,他引:3
S Demczuk C Baumberger B Mach J M Dayer 《The Journal of biological chemistry》1988,263(26):13039-13045
Cultured cells depend on cytokine mediators for sustained growth and maintenance and are routinely employed in bioassays to detect and measure minute changes in biological mediators, e.g. the interferons and interleukins. We evaluated the effects of mycoplasma infection on the steady-state mRNA levels of two cytokines IL-1 alpha and beta. Noninfected human squamous carcinoma cell line A431 expressed constitutively IL-1 alpha and beta mRNA. In contrast freshly isolated peripheral blood mononuclear cells and the monocytic cell line U937 expressed abundant IL-1 mRNA only after the appropriate stimulation. Peripheral blood mononuclear cells and U937 steady-state IL-1 beta mRNA levels were considerably greater than IL-1 alpha mRNA levels, whereas nearly equivalent high levels of IL-1 alpha and beta mRNA were detected in A431 cells. Mycoplasma infection of cultured A431 cells reduced the steady-state levels of IL-1 alpha and beta mRNA. This effect was nonspecific for A431 cells as actin mRNA steady-state levels showed similar decreases to mycoplasma contamination. However, this response was cell specific since mycoplasma-free and contaminated U937 cells differed little in IL-1 mRNA expression. These results show that the response to mycoplasma infection is at least partly cell-type dependent. 相似文献
55.
Peter WH Holland 《Genome biology》2000,1(4):reports4017.1-reports40172
A report on the 'Nuclear architecture and control of gene expression' minisymposium at the first meeting of the European Life Scientists Organisation (ELSO), Geneva, Switzerland, September 2-6, 2000. 相似文献
56.
Human red and green visual pigment genes are X-linked duplicate genes. To
study their evolutionary history, introns 2 and 4 (1,987 and 1,552 bp,
respectively) of human red and green pigment genes were sequenced.
Surprisingly, we found that intron 4 sequences of these two genes are
identical and that the intron 2 sequences differ by only 0.3%. The low
divergences are unexpected because the duplication event producing the two
genes is believed to have occurred before the separation of the human and
Old World monkey (OWM) lineages. Indeed, the divergences in the two introns
are significantly lower than both the synonymous divergence (3.2% +/- 1.1%)
and the nonsynonymous divergence (2.0% +/- 0.5%) in the coding sequences
(exons 1-6). A comparison of partial sequences of exons 4 and 5 of human
and OWM red and green pigment genes supports the hypothesis that the gene
duplication occurred before the human-OWM split. In conclusion, the high
similarities in the two intron sequences might be due to very recent gene
conversion, probably during evolution of the human lineage.
相似文献
57.
Nuno A Fonseca Cristina P Vieira Peter WH Holland Jorge Vieira 《BMC evolutionary biology》2008,8(1):200
Background
Although homeobox genes have been the subject of many studies, little is known about the main amino acid changes that occurred early in the evolution of genes belonging to different classes. 相似文献58.
59.
The consumption of fermented foods contaminated with aflatoxin B1 is linked to aflatoxicosis. Aflatoxicosis is a serious problem in developing countries with environmental conditions appropriate for the biosynthesis of AFB1 byAspergillus flavus andAspergillus parasiticus. In Africa, especially in Ghana and Nigeria, there is a very high risk of liver cancer which is caused by the consumption of AFB1-intoxicated, traditionally fermented maize and sorghum products. It is suggested that one way to diminish this health risk might be the reduction of the AFB1 concentration in foods by bacteria. Especially bacteria used for food fermentation processes are of great importance, with a special emphasis on lactic acid bacteria which are involved in traditionally fermented African foods based on maize and sorghum.Most publications dealing with aflatoxin degradation by microorganisms describe a phosphate buffer test system for the performance of degradation experiments. In contrast to that, a test system based on physiological active bacterial and yeast cells has been developed, to assess food fermentation organisms for their ability to reduce the AFB1 concentration in vitro. The aflatoxin B1 concentration in test samples was quatitatively determined by HPLC.The assessment of lactic acid bacteria originating from different German and other European culture collections only showed a very slight reduction of the AFB1 concentration from 3% to 12%. Screening experiments in which other bacterial genera and lactic acid bacteria, isolated from different African foods have been assessed, in most cases showed the same results. However, some bacterial strains, e.g. strains of the genusBacillus derived from European culture collections and strains of the genusLactobacillus isolated from African foods, caused a release of AFB1 which was chemically bound before to components of the test medium and which therefore could not be extracted with chloroform.A process quite similar to that may happen during food fermentations. Different experiments showed that e.g. cellulose can bind AFB1 very effectively. Cellulose and different other food components are well known to absorb AFB1. During fermentation the cellulose and other AFB1-absorbing components may be degraded and the AFB1 will be released again.The only bacterial strain known as yet which is able to reduce the AFB1 concentration in vitro and in different food comodities isNocardia corynebacteroides (formerFlavobacterium aurantiacum). Nevertheless the mechanism of this AFB1 reduction is actually not well understood, it still has to be investigated. In the meantime several other bacterial strains, presumably from the taxonomic group of theActinomycetes could be proved to be effective reducers of the AFB1 concentration in our in vitro test system. Because as yet no food relevant microorganism could be found, which is able to degrade AFB1, these new strains in general offer the possibility for a genetic modification of food relevant microorganisms. This seems to be the way to come to starter cultures which are able to degrade AFB1 during food fermentations. 相似文献
60.