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1.
Nathan D. Mathewson Orr Ashenberg Itay Tirosh Simon Gritsch Elizabeth M. Perez Sascha Marx Livnat Jerby-Arnon Rony Chanoch-Myers Toshiro Hara Alyssa R. Richman Yoshinaga Ito Jason Pyrdol Mirco Friedrich Kathrin Schumann Michael J. Poitras Prafulla C. Gokhale L. Nicolas Gonzalez Castro Marni E. Shore Kai W. Wucherpfennig 《Cell》2021,184(5):1281-1298.e26
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The basis for the apparent cooperativity in the activation of protein kinase C by phosphatidylserine has been addressed using proteolytic sensitivity, resonance energy transfer, and enzymatic activity. We show that binding of protein kinase C to detergent-lipid mixed micelles and model membranes is cooperatively regulated by phosphatidylserine. The sigmoidal dependence on phosphatidylserine for binding is indistinguishable from that observed for the activation of the kinase by this lipid [Newton & Koshland (1989) J. Biol. Chem. 264, 14909-14915]. Thus, protein kinase C activity is linearly related to the amount of phosphatidylserine bound. Furthermore, under conditions where protein kinase C is bound to micelles at all lipid concentrations, activation of the enzyme continues to display a sigmoidal dependence on the phosphatidylserine content of the micelle. This indicates that the apparent cooperativity in binding does not arise because protein kinase C senses a higher concentration of phosphatidylserine once recruited to the micelle. Our results reveal that the affinity of protein kinase C for phosphatidylserine increases as more of this lipid binds, supporting the hypothesis that a domain of phosphatidylserine is cooperatively sequestered around the enzyme. 相似文献
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J. T. Arnason G. J. Bourque C. Madhosilngh W. Orr 《Biochemical Systematics and Ecology》1986,14(6):569-574
The acetylenic allelochemical, phenylheptatriyne (PHT), from species of the Asteraceae disrupts membrane function in Fusarium culmorum by both phototoxic and non-phototoxic mechanisms. Treatment of mycelia or macroconidia with 10 ppm PHT leads to an aggregation of lipids visible in Sudan Black stained material. This characteristic stress response increases in conjunction with photosensitizing wavelengths of radiation (near UV). Mild treatment of PHT (10 ppm) and near UV (5 Wm2/50 min) inhibit 14C phenylalanine uptake and respiration and enhance K1 leakage suggesting that the membrane is the primary site of action of PHT. 相似文献
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The roles of specific and nonspecific interactions in the regulation of protein kinase C by lipid have been examined. Binding and activity measurements reveal two mechanisms by which protein kinase C interacts with membranes: (1) a specific binding to the activating lipid phosphatidylserine and (2) a nonspecific binding to nonactivating, acidic lipids. The specific interaction with phosphatidylserine is relatively insensitive to ionic strength, surface charge, and the presence of nonactivating lipids. The two second messengers of the kinase, diacylglycerol and Ca2+, increase markedly the affinity of the kinase for phosphatidylserine. In contrast, the nonspecific interaction is sensitive to ionic strength and surface charge, and is unaffected by diacylglycerol. These results suggest that electrostatic interactions promote the binding of protein kinase C to membranes but the cooperative and selective binding of phosphatidylserine is the dominant driving force in a productive protein-lipid interaction. 相似文献
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M. Y. Orr 《Plant Ecology & Diversity》2013,6(1-4):281-285
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L L Engel P J Marshall J C Orr V N Reinhold P Carter 《Biomedical mass spectrometry》1978,5(10):582-586
The low resolution mass spectra of E-3,4-bis-(p-hydroxyphenyl)-hex-3-ene (diethylstilbestrol), E-[1,1,1-3H3]3,4-bis-(p-hydroxyphenyl)-hex-3-ene, E-2,3-bis-(p-hydroxyphenyl)-but-2-ene (dimethylstilbestrol), E,E-3,4-bis-(p-hydroxyphenyl)hexa-2,4-diene (dienestrol) and 3,4-bis-(p-hydroxyphenyl)-hexane (hexestrol) were examined as the parent compounds, their diacetates, dimethyl ethers, and bis-trimethylsilyl ethers. In addition, the mass spectra of the diethyl ether and the hexadeuteriodimethyl ether of E-3,4-bis-(p-hydroxyphenyl)-hex-3-ene were studied. Each compound gives rise to several sets of characteristic fragment ions associated with loss of alkyl groups, loss of aryl groups and rearrangements. An ion of m/e 165 (C13H9) was found in the spectra of all the compounds studied. With the aid of high resolution mass spectrometry empirical formulae were assigned to major ions of the free diphenols. 相似文献
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Chemotherapy, in conjunction with other methods of treatment, was used in 100 patients with invasive hydatidiform mole or choriocarcinoma following mole. When treatment was instituted within two to six months of the antecedent mole serious drug resistance was not encountered, drug toxicity was slight, the duration of treatment was comparatively short, and sustained remissions were obtained in 57 out of 60 patients. When the start of chemotherapy was delayed beyond six months drug resistance occurred in many instances, toxicity was often severe, the duration of treatment was much longer, and sustained remissions were obtained in 22 out of 40 patients.The practice of giving prophylactic chemotherapy to all patients with mole is not established as effective or safe. Differences in the social background to hydatidiform mole in different geographical areas may be such that conclusions based on evidence from one area are not necessarily applicable to another.Careful follow-up after mole remains essential, though present methods often fail to ensure recognition of choriocarcinoma while it is still curable. Standard qualitative and quantitative methods for detecting the continued excretion of chorionic gonadotrophin, though useful, are sometimes too insensitive. It is suggested that to supplement local arrangements some form of centralized or regionalized follow-up service based on notification of patients with hydatidiform mole, and making use of radioimmunoassays for chorionic gonadotrophin, could reduce deaths attributable to late diagnosis. 相似文献