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1.
K. Silberbauer H. Sinzinger Maya Winter W. Feigl F. Ring 《Cellular and molecular life sciences : CMLS》1978,34(11):1471-1472
Summary Morphological control of Moncada's bioassay for prostacyclin (PG I2) activity measurement shows that the activity depends not only on endothelium, but in important amounts on subendothelial tissue too. Therefore, it can be concluded that platelet thrombus formation after endothelial cell injury does not depend only on the PG I2-producing ability of the tissue. 相似文献
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Shimamura T Shiroishi M Weyand S Tsujimoto H Winter G Katritch V Abagyan R Cherezov V Liu W Han GW Kobayashi T Stevens RC Iwata S 《Nature》2011,475(7354):65-70
The biogenic amine histamine is an important pharmacological mediator involved in pathophysiological processes such as allergies and inflammations. Histamine H(1) receptor (H(1)R) antagonists are very effective drugs alleviating the symptoms of allergic reactions. Here we show the crystal structure of the H(1)R complex with doxepin, a first-generation H(1)R antagonist. Doxepin sits deep in the ligand-binding pocket and directly interacts with Trp?428(6.48), a highly conserved key residue in G-protein-coupled-receptor activation. This well-conserved pocket with mostly hydrophobic nature contributes to the low selectivity of the first-generation compounds. The pocket is associated with an anion-binding region occupied by a phosphate ion. Docking of various second-generation H(1)R antagonists reveals that the unique carboxyl group present in this class of compounds interacts with Lys?191(5.39) and/or Lys?179(ECL2), both of which form part of the anion-binding region. This region is not conserved in other aminergic receptors, demonstrating how minor differences in receptors lead to pronounced selectivity differences with small molecules. Our study sheds light on the molecular basis of H(1)R antagonist specificity against H(1)R. 相似文献
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Sex differences in gonadotrophin concentrations in infancy 总被引:2,自引:0,他引:2
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The recognition of transfer-RNA by their cognate aminoacyl-tRNA synthetases is the crucial step in the translation of the genetic code. In order to construct a structural model of the complex between the tyrosyl-tRNA synthetase (TyrTS) from Bacillus stearothermophilus and tRNATyr, 40 basic residues at the surface of the TyrTS dimer have been mutated by site-directed mutagenesis and heterodimers created in vitro by recombining subunits derived from different mutants. As reported here a cluster of basic residues (Arg 207-Lys 208) in the N-terminal domain of one TyrTS subunit interacts with the acceptor stem of tRNATyr and two separated clusters of basic residues (Arg 368-Arg 371; Arg 407-Arg 408-Lys 410-Lys 411) in the C-terminal domain of the other subunit interact with the anticodon arm. The TyrTS would thus clamp the tRNA in a fixed orientation. The precise alignment of the flexible... ACCA 3' end of the tRNA for attack on the tyrosyl adenylate is made by contacts closer to the catalytic groups of the enzyme, such as with Lys 151. 相似文献
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A single point mutation has been engineered in the tyrosyl-tRNA synthetase that improves its affinity (KM) for its substrate ATP by a factor of 100. In the crystal structure of the tyrosyl tRNA synthetase (of Bacillus stearothermophilus), the side-chain hydroxyl of Thr 51 appears to make a weak hydrogen bond with the AMP moiety of the substrate intermediate, tyrosyl adenylate. In the absence of substrate, however, the hydroxyl group should make a strong hydrogen bond with water which would favour dissociation of the enzyme-substrate complex. We have used oligodeoxynucleotide-directed mutagenesis to construct two point mutants at this site: one to remove the hydroxyl group (Thr 51 leads to Ala 51) and the other, in addition, to distort the local polypeptide backbone (Thr 51 leads to Pro 51). We report here that both mutants have increased activity (kcat/KM for ATP) but one mutant (Pro 51) shows a massive 25-fold increase due mainly to a lowered KM for ATP. This demonstrates dramatically the potential of in vitro mutagenesis for improving the affinity of an enzyme for its substrate. 相似文献
7.
I. Faredin A. Benkö M. Winter A. Botos 《Cellular and molecular life sciences : CMLS》1961,17(5):225-225
Zusammenfassung In Hunden mitGoldblatt-Hypertonie ist die Adrenalinkonzentration der Arterien stark erhöht, diejenige von Noradrenalin aber — verglichen mit den Werten der Kontrolltiere — erniedrigt. Die Adrenalinerhöhung in der Arterienwandung ist wahrscheinlich nicht die Ursache des Hochdruckes, da sie auch in Hunden ohne postoperative Blutdruckerhöhung gefunden wurde. 相似文献
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E. Caspi D. O. Lewis D. M. Piatak K. V. Thimann A. Winter 《Cellular and molecular life sciences : CMLS》1966,22(8):506-507
Résumé Un échantillon purifié de cholestérol-4-C14 a été absorbé par des feuilles de 2 plantes deDigitalis purpurea. Après 18 jours on a extrait les plantes et séparé les composés radioactifs. Environ 1% des métabolites globales a été constaté en forme de pregnénolone. Ainsi le cholestérol peut agir comme précurseur des stérols végétaux.
This work was supported by Grants No. CA-07137, No. A-5326 and No. FR-05528 from the U.S. Public Health Service, and No. G-21799 from the National Science Foundation. 相似文献
This work was supported by Grants No. CA-07137, No. A-5326 and No. FR-05528 from the U.S. Public Health Service, and No. G-21799 from the National Science Foundation. 相似文献
10.
E. Caspi D. O. Lewis D. M. Piatak K. V. Thiman A. Winter 《Cellular and molecular life sciences : CMLS》1966,22(12):856-856
Zusammenfassung Der bei der Bestrahlung mit ionisierenden Strahlen auftretende Sättigungseffekt, d.h. die Abweichung von der Linearität des Verhältnisses zwischen der Strahlendosis und der Zahl der geschädigten Molekeln bei höheren Dosisleistungen, wird unter Zugrundelegung eines einfachen Modells, welches sowohl die Erzeugung als auch die Rekombination der Strahlenschäden berücksichtigt, mathematisch beschrieben. 相似文献