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1.
Denys-Drash syndrome (DDS) is characterized by early onset nephropathy, pseudohermaphroditism in males and a high risk for developing Wilms' tumour (WT). The exact cause of DDS is unknown but germline mutations in the Wilms' tumour suppressor gene (WT1) have recently been described in the majority of DDS patients studied. These mutations occur de novo and are clustered around the zinc finger (ZF) coding exons of the WT1 gene. Analysis of exons 2–10 of the WT1 gene in constitutional DNA from five patients with DDS was carried out using the polymerase chain reaction (PCR) and direct DNA sequencing. In four out of the five patients, heterozygous germline mutations were found: a novel point mutation in exon 8 (ZF2) at codon 377 altering the wild-type histidine to arginine, and three previously described point mutations in exon 9 (ZF3) in the codons corresponding to amino acids 394Arg and 396Asp. In one patient, no mutations could be demonstrated. In three patients where parental DNA was available, the mutations were shown to have occurred de novo. Furthermore, since tumour DNA in two of these cases had lost the wild-type allele, polymorphic markers from the short arm of chromosome 11 were used to determine the parental origin of the mutant chromosome. In both cases, the mutant chromosome was shown to be of paternal origin. Since the majority of published WT1 mutations in DDS patients alter a RsrII restriction site in exon 9, we were able to perform PCR-based diagnosis in a female patient with early renal insufficiency and normal external genitalia. 相似文献
2.
A study was performed to investigate possible interactions by magnetic fields (MF) with the processes of initiation and promotion of chemically induced preneoplastic lesions in rat liver. Male Sprague-Dawley rats were subjected to a 70% partial hepatectomy followed after 24 h by i.p. injection of diethylnitrosamine (DENA) as a tumour initiator. Starting one week after the DENA-treatment phenobarbital (PB) was given to promote growth of enzymatically altered foci of liver cells. MF was applied immediately after the partial hepatectomy and continued until sacrifice after 12 weeks of PB exposure. Homogenous horizontal AC magnetic fields with a frequency of 50 Hz and flux densities of 0.5 μT or 0.5 mT were used. The rats coexposed with MF and DENA plus PB did not gain weight as much as the rats exposed to the chemical agents only. The MF-exposure also resulted in a slight reduction in size and numbers of the focal lesions. The results suggest an interaction of MF with the processes of chemical carcinogenesis either as a result of stress or depending on effects on the proliferation of preneoplastic cells. © 1993 Wiley-Liss, Inc. 相似文献
3.
Agneta Nordenskjöld Fredrik Hedborg Holger Luthman Magnus Nordenskjöld 《Human genetics》1993,92(3):296-298
The Beckwith-Wiedemann syndrome (BWS) is characterized by somatic overgrowth, developmental anomalies, and proneness to embryonic tumor development. The majority of cases are sporadic, but several families with an autosomal dominant mode of inheritance with variable expression and reduced penetrance have been described. In three such families, BWS has been linked to DNA markers for the insulin gene (INS) and H-ras on chromosome band 11p15. Two additional families with inherited BWS are described here. Linkage analysis has been performed with a highly informative marker for the tyrosine hydroxylase (TH) locus within the INS-IGF2 (insulin-like growth factor II)-TH gene cluser and confirms the previous observed linkage to this region (lod score 2.16 at = 0). Linkage analysis to TH provides a basis for informed genetic counselling and carrier detection in the hereditary form of the syndrome. Based on the hypothesis that IGF2 may be a candidate gene for BWS, we screened for mutations in the coding exons 7 and 9, but found no abnormalities in 5 unrelated BWS cases. 相似文献
4.
A total of 211 Acinetobacter strains (representing all currently recognized genomic species) were tested for 329 biochemical characters. Overall similarities of all strains were determined for 145 characters by numerical taxonomic techniques, the UPGMA algorithm and the S SM and the S J coefficients as measures of similarity. Seven clusters (two or more strains) and three unclustered strains were recovered at a similarity level of 80.0% ( S SM ). At this level a complete correspondence between phenotypic cluster and genomic species was found only for genomic species 12 ( Ac. radioresistens ). At higher similarity levels (84.0% to 84.6% ( S SM )), however, several subclusters were found, each representing a single genomic species. An exception were the strains belonging to the genetically closely related species of the Acinetobacter calcoaceticus-baumannii complex. These were recovered scattered in several subclusters. The degree of genomic relatedness between some DNA groups correlated with phenotypic similarities, especially for DNA group 8 ( Ac. lwoffii ) and 15 of Tjernberg and Ursing, and for DNA group 4 ( Ac. haemolyticus ) and 6.
For the majority of genomic species, two identification matrices were constructed consisting of 22 and 10 diagnostic characters, respectively. The correct identification rates for the matrices were 98.0% (22 tests) and 90.8% (10 tests) taking a Willcox probability >0.9. For unambiguous identification of some genomic species, however, additional methods (preferably DNA-DNA hybridization or ribotyping) should be used. 相似文献
For the majority of genomic species, two identification matrices were constructed consisting of 22 and 10 diagnostic characters, respectively. The correct identification rates for the matrices were 98.0% (22 tests) and 90.8% (10 tests) taking a Willcox probability >0.9. For unambiguous identification of some genomic species, however, additional methods (preferably DNA-DNA hybridization or ribotyping) should be used. 相似文献
5.
Martin Tjernberg 《Ecography》1981,4(1):12-19
During a five-year period, 1975–1979, a total of 2881 prey individuals of 65 prey species were collected at 162 golden eagle nests from northern Sweden and from the island of Gotland. In northern Sweden birds are taken in higher numbers than mammals but calculated as weight the two categories are of equal importance, The main prey during the breeding season are capercaillie, black grouse, willow grouse, ptarmigan, mountain hare and reindeer fawns which together form 91% of the total food biomass. The capercaillie and the black grouse are taken more in the southern part of the coniferous region than in the northern. In contrast, in northern areas, reindeer fawns are more preyed upon than in the South, Ptarmigan and willow grouse are the most commonly captured prey species in mountain areas. The total number of reindeer fawns taken (dead and/or alive) by the Swedish golden eagle population during one summer is estimated at 600 individuals. On Gotland the golden eagles take mammals more often than in its northern distribution area. Rabbit and hedgehog arc the most important species. 相似文献
6.
Agneta Nordberg 《Life sciences》1978,23(9):937-944
Kinetic parameters for high affinity [HA] uptake in synaptosomes from different mouse brain regions were investigated. Vmax was highest in the striatum [200 pmol.· mg protein?1 · 4 min?1], followed by the cortex [111 pmol · mg protein?1 · 4 min?1], hippocampus [63 pmol · mg protein?1 · 4 min?1], midbrain [21 pmol · mg protein?1 · 4 min?1] and, lowest, medulla oblongata [5 pmol · mg protein?1 · 4 min?1]. Km was about the same in all brain regions [0.9–1.4 μM]. No sign of HA uptake was detected in synaptosomes from the cerebellum. A clear relationship between Vmax for synaptosomal HA uptake of Ch and apparent turnover of ACh was found between the brain regions. Administration of oxotremorine [1 mg·kg?1 i.p.] decreased Vmax for HA uptake of Ch by 60% in the cortex and hippocampus, by 50% in the striatum and by 20% in the midbrain. This effect is in accordance with the previously observed marked decrease in turnover of ACh in these brain regions following oxotremorine treatment. 相似文献
7.
Agneta Oskarsson Katherine S. Squibb Bruce A. Fowler 《Biochemical and biophysical research communications》1982,104(1):290-298
Gel chromatography of kidney postmitochondrial fractions from control rats 2 hr after injection of 203Pb or after in vitro incubation with 203Pb disclosed the presence of two fractionated Pb-binding components plus binding in the void volume and total volume regions. The binding of Pb to the two components, with molecular weights of 11,500 and 63,000 daltons, was markedly decreased in Pb-pretreated rats. Sodium dodecyl sulfate-gel electrophoresis and autoradiography showed the presence of one major 203Pb band with an estimated molecular weight of 60,000 daltons. The 11,500-dalton peak did not incorporate 14C-leucine nor did concomitant administration of cycloheximide with the 203Pb inhibit incorporation of 203Pb activity, suggesting that the component is a preformed constituent of the kidney. In vitro incubation of brain, liver and lung postmitochondrial supernatants with 203Pb disclosed that these two binding components were also present in brain but not in liver or lung, suggesting a target tissue-specific localization for these Pb-binding macromolecules. 相似文献
8.
The anterio-posterior distribution of cholinergic receptor binding sites in human hippocampus (five parts) as well as the effect of age (age range 3 days - 85 years) on receptor properties has been studied. Muscarinic binding sites was measured using labelled quinuclidinyl benzilate (3H-QNB) as ligand and labelled tubocurarine (3H-TC) was used for measurement of nicotine-like binding sites.The highest number of 3H-QNB binding sites in human hippocampus was measured at 3 days and 3 weeks of age and the lowest at 82 years of age. The proportion of high and low affinity muscarinic binding sites respectively was about the same at all ages investigated.A decrease in 3H-QNB binding sites with age was found in the anterior parts of the hippocampus (age range 55–84 years). When individual data for number of 3H-TC binding sites were plotted against corresponding number of 3H-QNB binding sites a strong correlation was observed in most of the different regions of the hippocampus. 相似文献
9.
Nicastrin, presenilin, APH-1, and PEN-2 form active gamma-secretase complexes in mitochondria 总被引:10,自引:0,他引:10
Hansson CA Frykman S Farmery MR Tjernberg LO Nilsberth C Pursglove SE Ito A Winblad B Cowburn RF Thyberg J Ankarcrona M 《The Journal of biological chemistry》2004,279(49):51654-51660
Mitochondria are central in the regulation of cell death. Apart from providing the cell with ATP, mitochondria also harbor several death factors that are released upon apoptotic stimuli. Alterations in mitochondrial functions, increased oxidative stress, and neurons dying by apoptosis have been detected in Alzheimer's disease patients. These findings suggest that mitochondria may trigger the abnormal onset of neuronal cell death in Alzheimer's disease. We previously reported that presenilin 1 (PS1), which is often mutated in familial forms of Alzheimer's disease, is located in mitochondria and hypothesized that presenilin mutations may sensitize cells to apoptotic stimuli at the mitochondrial level. Presenilin forms an active gamma-secretase complex together with Nicastrin (NCT), APH-1, and PEN-2, which among other substrates cleaves the beta-amyloid precursor protein (beta-APP) generating the amyloid beta-peptide and the beta-APP intracellular domain. Here we have identified dual targeting sequences (for endoplasmic reticulum and mitochondria) in NCT and showed expression of NCT in mitochondria by immunoelectron microscopy. We also showed that NCT together with APH-1, PEN-2, and PS1 form a high molecular weight complex located in mitochondria. gamma-secretase activity in isolated mitochondria was demonstrated using C83 (alpha-secretase-cleaved C-terminal 83-residue beta-APP fragment from BD8 cells lacking presenilin and thus gamma-secretase activity) or recombinant C100-Flag (C-terminal 100-residue beta-APP fragment) as substrates. Both systems generated an APP intracellular domain, and the activity was inhibited by the gamma-secretase inhibitors l-685,458 or Compound E. This novel localization of NCT, PS1, APH-1, and PEN-2 expands the role and importance of gamma-secretase activity to mitochondria. 相似文献
10.
Sophie Githinji Samwel Kigen Dorothy Memusi Andrew Nyandigisi Agneta M. Mbithi Andrew Wamari Alex N. Muturi George Jagoe Jim Barrington Robert W. Snow Dejan Zurovac 《PloS one》2013,8(1)