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101.
Abstract The rationale for proposing the title compounds as potential adenosine diphosphate receptor antagonists is discussed. A convenient synthesis and formulation for the cyclopentenyl amino alcohol 8 is described. 相似文献
102.
Donald J. Dowbenko Herbert L. Ennis 《Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression》1982,696(2):218-222
Microcyst germination in Polysphondylium pallidum can be used as a model for studying gene expression because temporally regulated modulations in protein synthesis occur in this developmental pathway. Germinating cysts were labeled with [35S]methionine for half-hourly periods during the synchronous germination sequence, and the proteins labeled in each period were resolved by two-dimensional polyacrylamide gel electrophoresis. Three major classes of proteins observed were distinguished by the time of onset and duration of their synthesis: (a) proteins made throughout germination; (b) proteins synthesized only during a portion of the germination pathway; and (c) polypeptides whose synthesis started at 1 or 1.5 h and then continued throughout germination. 相似文献
103.
Multiple genetic mechanisms have contributed to the generation of the HLA-A2/A28 family of class I MHC molecules 总被引:7,自引:0,他引:7
N Holmes P Ennis A M Wan D W Denney P Parham 《Journal of immunology (Baltimore, Md. : 1950)》1987,139(3):936-941
The genetic events that produce diversity in class I MHC genes and proteins has been investigated by using a family of closely related HLA-A alleles. Five genes coding for HLA-A2.2Y, HLA-A2.3, and HLA-Aw68.2 have been isolated. Exon sequences are compared with the known sequences for HLA-A2.1, HLA-A2.2F, HLA-A2.4, HLA-Aw68.1, and HLA-Aw69. Pairwise comparison of the eight unique sequences shows that point mutation, reciprocal recombination, and gene conversion have all contributed significantly to the diversification of this family of alleles. These results are compared with those of other studies that have emphasized the role of gene conversion. A predominance of coding substitutions in the alpha 1 and alpha 2 domains is found, consistent with positive selection for polymorphism being a major factor in the fixation of these alleles. In the three cases examined, genes for phenotypically identical proteins gave identical nucleotide sequences, indicating that most, if not all, of the class I polymorphism is detectable by immunological methods. The apparent stability of the sequences suggests that the events generating some of the alleles occurred before the origin of modern Homo sapiens. 相似文献
104.
105.
Interaction of vernamycin A with Escherichia coli ribosomes 总被引:2,自引:0,他引:2
H L Ennis 《Biochemistry》1971,10(7):1265-1270
106.
Synthesis of macromolecules during microcyst germination in the cellular slime mold Polysphondylium pallidum 总被引:1,自引:0,他引:1
Microcyst germination in the cellular slime mold Polysphondylium pallidum is a useful model for studying macromolecular changes necessary for or coincident with the transition from one cell type (cyst) to another (amoebae). Protein synthesis starts soon after cysts are incubated under permissive conditions, as evidenced by the incorporation of precursors and the appearance of polysomes. Sodium dodecyl sulfate-polyacrylamide gel analysis of proteins made at intervals during germination shows that protein synthesis is developmentally regulated during this process. RNA synthesis also begins early during germination. Cysts contain polyadenylated RNA that can stimulate the incorporation of radioactive amino acids into protein in an in vitro wheat germ protein synthesizing system. The concentration of poly(A)-containing RNA increases during germination and during inhibition of protein synthesis by cycloheximide. 相似文献
107.
Veitch NJ Ennis M McAbney JP;US-Venezuela Collaborative Research Project Shelbourne PF Monckton DG 《DNA Repair》2007,6(6):789-796
Huntington disease (HD) is associated with an unstable trinucleotide CAG.CTG repeat expansion. Although the repeat length is inversely correlated with the age-at-onset of symptoms, variability between patients who have inherited the same HD repeat length clearly suggests that other factors influence this aspect of the disease. As repeat length profiles in somatic tissues suggest that repeat length gains may contribute to both the tissue-specificity and progressive nature of HD pathogenesis, genetic modifiers of mutation length variability may therefore influence the age-at-onset of the disease. Using a sensitive single molecule-PCR assay we show that HD mutation length profiles in buccal cell DNA vary from individual to individual. The resulting data provide the first quantitative evidence that inherited CAG.CTG repeat length has a major influence on somatic CAG.CTG repeat length variation. In addition, we confirm that further environmental and/or genetic modifiers of repeat length variation exist and discuss the implications that our results may have on understanding the factors that influence severity and age-at-onset of Huntington disease symptoms. 相似文献
108.
109.
Piperazinyl-glutamate-pyrimidines as potent P2Y12 antagonists for inhibition of platelet aggregation
John J. Parlow Mary W. Burney Brenda L. Case Thomas J. Girard Kerri A. Hall Ronald R. Hiebsch Rita M. Huff Rhonda M. Lachance Deborah A. Mischke Stephen R. Rapp Rhonda S. Woerndle Michael D. Ennis 《Bioorganic & medicinal chemistry letters》2009,19(21):6148-6156
Piperazinyl-glutamate-pyrimidines were prepared with oxygen, nitrogen, and sulfur substitution at the 4-position of the pyrimidine leading to highly potent P2Y12 antagonists. In particular, 4-substituted piperidine-4-pyrimidines provided compounds with exceptional potency. Pharmacokinetic and physicochemical properties were fine-tuned through modifications at the 4-position of the piperidine ring leading to compounds with good human PRP potency, selectivity, clearance and oral bioavailability. 相似文献
110.
John J. Parlow Mary W. Burney Brenda L. Case Thomas J. Girard Kerri A. Hall Ronald R. Hiebsch Rita M. Huff Rhonda M. Lachance Deborah A. Mischke Stephen R. Rapp Rhonda S. Woerndle Michael D. Ennis 《Bioorganic & medicinal chemistry letters》2009,19(16):4657-4663
Polymer-assisted solution-phase (PASP) parallel library synthesis was used to discover a piperazinyl-glutamate-pyridine as a P2Y12 antagonist. Exploitation of this lead provided compounds with excellent inhibition of platelet aggregation as measured in a human platelet rich plasma (PRP) assay. Pharmacokinetic and physiochemical properties were optimized leading to compound (4S)-4-[({4-[4-(methoxymethyl)piperidin-1-yl]-6-phenylpyridin-2-yl}carbonyl)amino]-5-oxo-5-{4-[(pentyloxy)carbonyl]piperazin-1-yl}pentanoic acid 22J with good human PRP potency, selectivity, in vivo efficacy and oral bioavailability. 相似文献