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In vivo chromosomal instability in ataxia-telangiectasia homozygotes and heterozygotes 总被引:1,自引:0,他引:1
Summary The exfoliated cell micronucleus test was used to monitor in vivo chromosomal instability in a population comprised of five ataxia-telangiectasia (A-T) homozygotes and seven obligate heterozygotes (parents of A-T patients). This assay was previously validated as a procedure for quantifying non-invasively carcinogen-induced chromosomal aberrations occurring in vivo in epithelial tissues of both the oral cavity and the urinary bladder. The procedure involved taking airdried smears of three sites in the oral cavity of each examined individual. Desquamated urinary bladder cells were collected by centrifugation of freshly voided urine samples. Frequencies of exfoliated cells in these preparations were determined and compared with control values (individuals with no genetic chromosomal instability and no known carcinogene exposure) for these sites. Exforliated cell micronucleus (MEC) frequencies were elevated 5- to 14-fold in samples from the A-T homozygotes. This elevation in MEC frequency occurred for both the oral cavity and urinary bladder. Five out of the seven obligate A-T heterozygotes had an elevated MEC frequency in samples from the oral cavity. In addition, all examined urine samples from A-T heterozygotes contained an elevated percentage of micronucleated cells. These data suggest that this assay is suitable for in vivo monitoring of groups of individuals in which genetically produced chromosomal damage occurs. The possibility of A-T heterozygote detection with this simple procedure is of particular significance, since such individuals are believed to comprise up to 1% of the general population, and have been identified as being at elevated risk for cancer. 相似文献
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The Salmonella/microsome mutagenesis assay was used to determine the effect of cysteine (alpha-amino-beta-mercaptopropionic acid) on the mutagenic actions of several carcinogens: N-methyl-N'-nitro-N-nitrosoguanidine. N-acetoxy-2-acetylaminofluorene, N-hydroxy-2-acetylaminofluorene, 4-nitroquinoline-1-oxide, methyl methanesulfonate, 5-nitro-2-furaldehyde semicarbazone, 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide, aflatoxin B1 and the nitrosation products of methylurea and methylguanidine. Cysteine, at non-toxic concentrations, significantly decreased the frequency of reversion to histidine prototrophy when it was added to treatment mixtures. The extent of the inhibition of mutagenic action by cysteine depended on the carcinogen studied as well as the doses of cysteine and carcinogen employed. Cysteine (2.5--10 mM) completely inhibited the mutagenic actions of N-methyl-N'-nitro-N-nitrosoguanidine and methylguanidine nitrosation products while only partially preventing the mutagenic effects of the other carcinogens assayed. Inhibition of 5-nitro-2-furaldehyde semicarbazone-induced mutagenesis occurred only with higher cysteine concentrations (20--200 mM). 相似文献
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Mitotic gene conversion in the D7 strain of Saccharomyces cerevisiae was significantly enhanced by exposure to non-enzymatic browning reaction products. These products were formed during the heating of sugar (caramelization reaction) or sugar-amino acid mixtures (Maillard reaction) at temperatures normally used during the cooking of food. Several modulating factors of this convertogenic activity were identified. These factors included two main groups: (1) trace metals which are widely distributed in the environment; and (2) several cellular enzymatic systems. The convertogenic activities of a heated glucose-lysine mixture and a commercial caramel powder were completely suppresses when yeast were concurrently exposed to these products and to either FeIII or CuII. Equimolar concentrations of MnII or sodium selenite had no effect on the convertogenic activity of the products of either model system. Horse-radish peroxidase, beef liver catalase and rat liver S9 preparations each decreased the frequency of gene conversion induced by the caramel powder and the heated glucose-lysine products. This modulating activity of the enzymes was lost if they were heat-inactivated. These studies indicate the presence of a variety of protective mechanisms which can modify genotoxic components in complex food mixtures. 相似文献
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Evidence for chromosome instability in vivo in bloom syndrome: Increased numbers of micronuclei in exfoliated cells 总被引:1,自引:0,他引:1
Summary The incidence of exfoliated epithelial cells containing micronuclei was determined in two small human populations, one homozygous
and the other heterozygous for the Bloom syndrome gene (bl). The objectives of the study were two: (1) to learn whether the chromosome instability featured so prominently by Bloom
syndrome (BS) cells proliferating in vitro also occurs in vivo, and (2) as part of a broad survey of various cancer-prone
populations, to determine whether estimating micronucleus frequencies in exfoliated cell samples might be useful for identifying
individuals with genetically determined chromosome instability. Eight individuals homozygous (bl/bl) for the BS gene, i.e., persons with the clinical syndrome, were examined, along with 11 obligate heterozygotes (bl/+), parents of affected persons. Exfoliated cells were obtained from two sites, the oral cavity and the urinary tract. Striking
and statistically highly significant elevations in the frequencies of cells with micronuclei were observed in cells from both
sites in bl/bl individuals compared to that in bl/+ (P<0.001) and in a control population, indicating that chromosome instability occurs in vivo in BS. In contrast, micronucleus
frequencies at either site did not differ significantly between bl/+ individuals and the control population. This survey, in combination with similar earlier ones of populations predisposed
to cancer not on a genetic basis but because of exposure to some environmental carcinogen, suggests that the exfoliated cell
micronucleus test identifies individuals whose somatic genetic material has, for either genetic or environmental reasons,
been damaged in a way that produces chromosome breakage and rearrangement. 相似文献
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Stephen D. Skaper Nicholas A. Evans Peter E. Soden Claudia Rosin Laura Facci Jill C. Richardson 《Neurochemical research》2009,34(12):2243-2250
Alzheimer’s disease is characterised by regional neuronal degeneration, synaptic loss, and the progressive deposition of the
4 kDa β-amyloid peptide (Aβ) in senile plaques and accumulation of tau protein as neurofibrillary tangles. Aβ derives from
the larger precursor molecule, amyloid precursor protein (APP) by proteolytic processing via β- and γ-secretases. While APP
expression is well documented in neurons and astrocytes, the case for oligodendrocytes is less clear. The latter cell type
is reported to express different isoforms of APP, and we have confirmed this observation by immunocytochemistry in cultures
of differentiated rat cortical oligodendrocytes. Moreover, by means of a sensitive electrochemiluminescent immunoassay employing
Aβ C-terminal specific antibodies, mature oligodendrocytes are shown to secrete the 40 and 42 amino acid Aβ species (Aβ40
and Aβ42). Secretion of Aβ peptides was reduced by incubating oligodendrocytes with α- and β-secretase inhibitors, or a γ-secretase
inhibitor. Disturbances of APP processing and/or synthesis in oligodendrocytes may account for some myelin disorders observed
in Alzheimer’s disease and other senile dementias. 相似文献
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