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111.
Folylpoly-gamma-glutamate synthetase (FPGS, EC 6.3.2.17) catalyzes the ATP-dependent ligation of glutamic acid to reduced folates including (6S)-5,6,7,8-tetrahydrofolate (H4PteGlu), as well as to anticancer drugs such as 5,10-dideaza-5,6,7,8-tetrahydrofolate ((6R)-DDAH4PteGlu1, (6R)-DDATHF, Lometrexol). Synthesis of unlabeled mono- and polyglutamates, DDAH4PteGlu(n) (6R, n = 1-6; 6S, n = 1-2), as well as (6R)-DDAH4Pte[14C]Glu1, was effected from (6R)- or (6S)-5,10-dideazatetrahydropteroyl azide and glutamic acid, H-Glu-gamma-Glu(n)-gamma-Glu-OH (n = 0-4), or [14C]glutamic acid, respectively. These compounds were evaluated as FPGS substrates to determine steady-state kinetic constants. Michaelis-Menten kinetics were observed for (6R)-DDAH4PteGlu1, the isomer corresponding to H(4)PteGlu, whereas marked substrate inhibition was observed for (6S)-DDAH4PteGlu(n) (n = 1-2) and (6R)-DDAH4PteGlu(n) (n = 2-5), but not (6R)-DDAH4PteGlu6. Multiple ligation of glutamate renders a quantitative analysis of these data difficult. However, approximate values of K(M) = 0.65-1.6 microM and K(I) = 144-417 microM for DDAH4PteGlu(n) were obtained using a simple kinetic model. 相似文献
112.
Neil M. Boag Kathleen M. Coward Anthony C. Jones Martyn E. Pemble J. Robin Thompson 《Acta Crystallographica. Section C, Structural Chemistry》2000,56(12):1438-1439
The hydrolysis product [Ga2(C3H7)4(OH)2]·C14H32N4, derived from the tetrakis(triisopropylgallium)–1,4,8,11‐tetramethyl‐1,4,8,11‐tetraazacyclotetradecane (1/1) adduct, consists of a centrosymmetric [iPr2Ga(μ‐OH)]2 unit hydrogen bonded through the hydroxyl group to a nitrogen on an adjacent centrosymmetric 1,4,8,11‐tetramethyl‐1,4,8,11‐tetraazacyclotetradecane molecule, resulting in the generation of a molecular chain through the crystal. 相似文献
113.
Jackson SJ Bluck LJ Coward WA 《Rapid communications in mass spectrometry : RCM》2004,18(10):1003-1007
It has been proposed that the (13)C-octanoic acid breath test (OBT) provides a safe, non-radioactive means of measuring gastric emptying. However, deuterated octanoic acid provides a better marker when compared with scintigraphy, as the kinetics are less complex than those of the (13)C label. The appearance of (2)H in saliva is modelled as a two-compartment body water system, using an asymmetric triangular gastric emptying function. This study compared the (2)H-octanoic acid saliva test (OST) with the OBT in measuring altered states of gastric emptying in the nutritional context of diet manipulation. Gastric emptying was measured using the OST and OBT in a three-way crossover study involving 12 healthy male and female subjects (mean BMI = 23.4 kg/m(2), aged 24-57 years). Following an overnight fast, subjects were given an egg meal, labelled with 10 microL/kg body weight (2)H-octanoic acid and 100 microL (13)C-octanoic acid. The meal was nutritionally manipulated to provide a 1 MJ, 2 MJ or 3 MJ meal. Breath and saliva samples were collected at regular intervals for 6 h, with further saliva samples being collected over four subsequent days. (2)H isotopic enrichment in saliva and (13)C isotopic enrichment in breath were analysed using isotope ratio mass spectrometry and the data fitted to the respective gastric emptying models. The half excretion time (T(1/2) (D)), time to maximum emptying rate (T(1) (D)) and time when emptying is complete (T(2) (D)) were calculated from the (2)H saliva test data, and the lag time (T(lag) (C)), half excretion time (T(1/2) (C)), latency phase (T(lat) (C)) and ascension time (T(asc) (C)) were calculated from the (13)C breath test data. Overall, the OBT correlated well with the OST, with a significant relationship between T(1/2) (C) and T(1/2) (D), a significant relationship between T(lat) (C) and T(1) (D) and finally a significant relationship between T(asc) (C) and T(2) (D). Gastric emptying measured using the OST was significantly faster with the 1 MJ meal (DeltaT(1/2) (D) = -0.77 h vs. 2 MJ, p = 0.004). Increases were also seen when the meal size was increased from 2 MJ to 3 MJ (DeltaT(1/2) (D) = +0.44 h vs. 2 MJ), but these were not significant. These trends were mirrored in the OBT data, with significant differences between 1 MJ and 2 MJ (DeltaT(1/2) (C) = -0.63 h vs. 2 MJ, p = 0.013) and non-significant increases with the larger 3 MJ meal (DeltaT(1/2) (C) = +0.10 h vs. 2 MJ). Total meal calorie content was shown to have an effect on gastric emptying using both the OBT and the OST. The deuterium method allows the direct calculation of the gastric emptying function and could be used as an alternative to gamma scintigraphy, allowing further validation of the (13)C-octanoic acid breath test. 相似文献
114.
Marijke WA de Backer Maike AD Brans Mieneke CM Luijendijk Keith M Garner Dianne MA van den Heuvel R Jeroen Pasterkamp Roger AH Adan 《BMC neuroscience》2010,11(1):94
Background
Multiple neuropeptides, sometimes with opposing functions, can be produced from one precursor gene. To study the roles of the different neuropeptides encoded by one large precursor we developed a method to overexpress minigenes and establish local secretion. 相似文献115.
116.
R. Albrecht T. C. Awes C. Baktash P. Beckmann F. Berger R. Bock G. Classon L. Dragon R. L. Ferguson A. Franz S. Garpman R. Glasow H. A. Gustafsson H. H. Gutbrod K. H. Kampert B. W. Kolb P. Pristiansson I. Y. Lee H. L?hner I. Lund F. E. Obenshain A. Oskarsson I. Ottrlund T. Peitzmann S. Persson F. Plasil A. M. Poskanzer M. Purschke H. G. Ritter R. Santo H. R. Schmidt T. Siemiarczuk S. P. Sorensen E. Stenlung G. R. Young WA Collaboration 《Zeitschrift fur Physik C Particles and Fields》1988,38(1):97-103
Transverse momentum (p T) distributions fo inclusive photons and neutral pions at midrapidity are measured with a lead glass calorimeter in 60 and are measured with a lead glass calorimeter in 60 and 200A·Gev16O+nucleus and and proton+nucleus reactions. Inclusive photon distributions are compared for central and peripheral reactions. The degree of centrality is determined either from the charged particle multiplicity or from the remaining projectile energy in the forward direction. Deviations from a nucleus+nucleus interaction model based upon linear extrapolation from p+p reactions are observed in central16O+Au data. The variation of theaverage transverse momentum is investigated as function of centrality. The target-mass and energy dependence of π0 p T distributions are presented. For16O+Au a change of slope in these distributions is observed atp t ≈0.8 GeV/c compatible with hydrodynamic expansion models. 相似文献
117.
Becker JJ Blaylock GT Bolton T Brown JS Bunnell KO Burnett TH Cassell RE Coffman D Cook V Coward DH Dorfan DE Dubois GP Duncan AL Eigen G Einsweiler KF Eisenstein BI Freese T Gladding G Grancagnolo F Grab C Hamilton RP Hauser J Heusch CA Hitlin DG Köpke L Li A Lockman WS Mallik U Matthews CG Mockett PM Mozley RF Nemati B Odian A Partridge R Perrier J Pitman D Plaetzer SA Richman JD Sadrozinski HF Scarlatella M Schalk TL Schindler RH Seiden A Simopoulos C Spadafora AL Stockdale IE Stockhausen W 《Physical review letters》1987,59(2):186-189
118.
Baltrusaitis RM Becker JJ Blaylock GT Bolton T Brown JS Bunnell KO Burnett TH Cassell RE Coffman D Cook V Coward DH Cui H Dado S Del Papa C Dorfan DE Dubois GP Duncan AL Eigen G Einsweiler KF Eisenstein BI Fabrizio R Favart D Gladding G Grancagnolo F Guy AD Hamilton RP Hauser J Heusch CA Hitlin DG Köpke L Lockman WS Mallik U Matthews CG Mockett PM Moss L Mozley RF Nappi A Nemati B Odian A Partridge R Perrier J Plaetzer SA Richman JD Roehrig J Russell JJ Sadrozinski HF Scarlatella M Schalk TL 《Physical review letters》1986,56(2):107-110
119.
120.
2-Amino-5-[p- (bromoacetamidomethyl)benzenesulfonamidopropyl]-6-methyl-4-pyrimidinol (XV) was synthesized by acylation of 2-amino-5-aminopropyl-6-methyl-4-pyrimidinol (III) with p-cyanobenzenesulfonyl chloride followed by catalytic reduction and reaction of the resultant aminomethyl group with p-nitrophenyl bromoacetate. A second irreversible inhibitor of thymidylate synthetase, namely 2-amino-5-[p-(bromoacetyl)benzene-sulfonamidopropyl]-6-methyl-4-pyrimidinol (XVI), was synthesized by acylation of in with p-acetylbenzenesulfonyl chloride followed by bromination. Both XV and XVI were good reversible inhibitors of thymidylate synthetase and inactivated the enzyme when the candidate compound was incubated with the enzyme. Iodoacetamide, which does not form a complex with enzyme, could inactivate thymidylate synthetase almost as well as XV; therefore it appears that XV inactivated the enzyme by a random bimolecular mechanism rather than by the desired active-site-directed mechanism via an enzyme-inhibitor complex. Similar conclusions were reached with XVI since phenacyl bromide could inactivate the enzyme somewhat more rapidly than XVI. 相似文献