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31.
Regulation of oxidative phosphorylation: The flexible respiratory network ofParacoccus denitrificans
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APC mutation in the alternatively spliced region of exon 9 associated with late onset familial adenomatous polyposis 总被引:11,自引:0,他引:11
Rob B. van der Luijt Hans F. A. Vasen Carli M. J. Tops Cor Breukel Riccardo Fodde P. Meera Khan 《Human genetics》1995,96(6):705-710
Germ-line mutations in the adenomatous polyposis coli (APC) gene are responsible for familial adenomatous polyposis (FAP). Genotype-phenotype correlation studies in patients with FAP have demonstrated associations of certain variants of the disease with mutations at specific sites within the APC gene. In a large FAP family, we identified a frameshift mutation located in the alternatively spliced region of exon 9. Phenotypic studies of affected family members showed that the clinical course of FAP was delayed, with gastrointestinal symptoms and death from colorectal carcinoma occurring on average 25 and 20 years later than usual, respectively. The numbers of colorectal adenomas differed markedly among affected individuals and the location of colorectal cancer lay frequently in the proximal colon. Our findings suggest that the exon 9 mutation identified in the pedigree is associated with late onset of FAP. The atypical phenotype may be explained by the site of the mutation in the APC gene. Analysis of the APC protein product indicated that the exon 9 mutation did not result in a detectable truncated APC protein. Given the location of the mutation within an alternatively spliced exon of APC, it is conceivable that normal APC proteins are produced from the mutant allele by alternative splicing. 相似文献
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Corien C. Verschuuren-Bemelmans Ewout R. P. Brunt Margaret Burton Rob G. J. Mensink Martin A. van der Meulen Nico H. Smit Irene Stolte-Dijkstra Charles H. C. M. Buys Hans Scheffer 《Human genetics》1995,96(6):691-694
The autosomal dominant cerebellar ataxias (ADCA) are clinically and genetically heterogeneous. To date, several loci (SCAI-V) have been identified for ADCA type I. We have studied two large families from the northern part of The Netherlands with ADCA type I with a broad intra-familial variation of symptoms. In both families significant linkage is shown of the disease to the markers of the SCA3 locus on chromosome 14. Through recombinations, the candidate region for SCA3 could be refined to a 13-cM range between D14S256 and D14S81. No recombinations were detected with the markers D14S291 and D14S280, which suggests that the SCA3 gene lies close to these loci. This finding will benefit the individuals at risk in these two families who are seeking predictive testing or prenatal diagnosis. 相似文献
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Ronald J. Ash Gary A. Flynn Rob M.J. Liskamp Harry C.J. Ottenheijm 《Biochemical and biophysical research communications》1984,125(2):784-789
Sparsomycin, ScRs configuration, was the most potent of the four possible stereoisomers as a competitive inhibitor of peptide bond formation. In addition, the configuration of the two chiral centers dictated whether the compound exhibited time- and temperature-dependent inhibition of peptidyl transferase when incubated with polysomes prior to enzyme assay. The data corroborate the thesis that a peptidyl transferase-mediated acylation of the pivotal sulfoxide moiety and subsequent Pummerer rearrangement play a significant role in the inhibitory properties of sparsomycin. 相似文献
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Rob H. M. Ebberink Albertus de Zwaan 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1980,137(2):165-171
Summary Concentrations of glycolytic intermediates, lactate, adenine nucleotides, inorganic phosphate, phosphoarginine and citrate have been estimated after various periods of valve closure (Table 1 and Fig. 1). Mass action ratios of enzyme steps involved in the metabolism of these components are compared with their equilibrium constants. This reveals glycogen phosphorylase, phosphofructokinase, hexosediphosphatase and pyruvate kinase catalyze non-equilibrium reactions. The first three enzymes possess relatively low activities (Table 2).From the changes in concentrations of the glycolytic intermediates it is concluded that phosphofructokinase controls the carbon flow during the first hours after valve closure, whereas later on the rate of conversion of phosphoenolpyruvate is determining this flow. In skeletal muscle phosphofructokinase controls the carbon flow during the whole period of exercise.The concentrations of ADP, AMP and inorganic phosphate increase, whereas the concentrations of ATP, phosphoarginine and citrate decrease during valve closure (Table 1 and Fig. 2). In contrast to skeletal muscle, these changes do not result in a strong increase in the glycolytic flux.There is a much greater potential for ATP hydrolysis by the myofibrillar ATPase system than is actually realized by the adductor muscle during valve closure. 相似文献
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Corneal epithelial cells have been used to study cell surface changes during cell aggregation. Tissue was taken from developmental stages in which desmosomes were forming rapidly. When corneal cells are dispersed, adjacent desmosome plaques are separated and single plaques are left on the cell surface. As cells aggregate, changes in the frequency of single plaques or of full desmosomes (double plaques) per micrometer of cell surface cross section can be followed. Single plaques are lost from the surface by endocytosis. Quantitative studies show a loss of single plaques beginning in the first hour of culture and formation of double plaques at 2 to 3 hr. In cells treated with cytochalasin B or D, single plaques are not lost during the first 2 hr and double plaques form with a higher frequency. Formation of double plaques is suppressed by actinomycin D, cycloheximide, and dinitrophenol. Thus desmosome formation requires de novo protein synthesis. In addition, inhibition of cell surface turnover by drugs which modify the cytoskeleton will enhance the rate at which desmosomes form. 相似文献
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Summary About one third of the Dutch environmental research is concentrated on aquatic problems. The largest number of these projects is physicochemical (65%) and 47% of the aquatic projects contains an ecological component. The aquatic research projects are executed in a large number of different research institutes. Many institutes just formulated one project (43.2%) and about 10% of the institutes formulated 10 projects. The institutes with 10 or more projects account for almost 50% of the total number of projects. However, the size of the research projects with respect to the average total personnel per year may differ considerably. The largest number of aquatic research projects is carried out in governmental institutes. This relative high share of governmental institutes has proportionally increased during the period of 1975–1982. During this period the relative shares of all the aquatic research projects with an ecological component, of the strictly ecological projects and of the ecological/physicochemical projects have also proportionally inclined. However, in absolute numbers there seems to be a decline of both ecological and non-ecological projects on aquatic problems. 相似文献
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