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81.
Microsomal cytochrome P450 and eicosanoid metabolism 总被引:1,自引:0,他引:1
The demonstration of a role for microsomal P450 in the metabolism of endogenous pools of arachidonic acid established this
enzyme system as a member of the arachidonic acid cascade and characterized a new an important metabolic function for this
enzyme system. Studies from several laboratories documenting the powerful biological activities of the P450-derived eicosanoids
have suggested important roles for the P450 arachidonic acid monooxygenase in renal and vascular physiology, and in the pathophysiology
of experimental hypertension. These studies provide significant evidence to indicate that in addition to its recognized traditional
toxicological and pharmacological roles, microsomal P450s also play important physiological roles in the control of tissue
and body homeostasis. 相似文献
82.
Quantum annealing with manufactured spins 总被引:1,自引:0,他引:1
Johnson MW Amin MH Gildert S Lanting T Hamze F Dickson N Harris R Berkley AJ Johansson J Bunyk P Chapple EM Enderud C Hilton JP Karimi K Ladizinsky E Ladizinsky N Oh T Perminov I Rich C Thom MC Tolkacheva E Truncik CJ Uchaikin S Wang J Wilson B Rose G 《Nature》2011,473(7346):194-198
Many interesting but practically intractable problems can be reduced to that of finding the ground state of a system of interacting spins; however, finding such a ground state remains computationally difficult. It is believed that the ground state of some naturally occurring spin systems can be effectively attained through a process called quantum annealing. If it could be harnessed, quantum annealing might improve on known methods for solving certain types of problem. However, physical investigation of quantum annealing has been largely confined to microscopic spins in condensed-matter systems. Here we use quantum annealing to find the ground state of an artificial Ising spin system comprising an array of eight superconducting flux quantum bits with programmable spin-spin couplings. We observe a clear signature of quantum annealing, distinguishable from classical thermal annealing through the temperature dependence of the time at which the system dynamics freezes. Our implementation can be configured in situ to realize a wide variety of different spin networks, each of which can be monitored as it moves towards a low-energy configuration. This programmable artificial spin network bridges the gap between the theoretical study of ideal isolated spin networks and the experimental investigation of bulk magnetic samples. Moreover, with an increased number of spins, such a system may provide a practical physical means to implement a quantum algorithm, possibly allowing more-effective approaches to solving certain classes of hard combinatorial optimization problems. 相似文献
83.
P. S. Bhathal S. L. Ho M. P. Hegarty Roger L. N. Harris 《Cellular and molecular life sciences : CMLS》1984,40(8):894-896
Summary Chronic active hepatitis was selectively induced in mice by the feeding of a diet containing 3-hydroxy-4-pyrone (0.5% by weight) for periods of 6 weeks and longer. This model should be of particular value in elucidating the pathogenesis of drug-induced forms of chronic active hepatitis. Maltol (3-hydroxy-2-methyl-4-pyrone) did not produce any liver lesion.Acknowledgment. This research was supported in part by a grant from the Sir A.E. Rowden White Bequest to the Department of Pathology, University of Melbourne.To whom correspondance and requests for reprints should be addressed. 相似文献
84.
S B England L V Nicholson M A Johnson S M Forrest D R Love E E Zubrzycka-Gaarn D E Bulman J B Harris K E Davies 《Nature》1990,343(6254):180-182
85.
86.
K. Prabhakaran E.B. Harris W.F. Kirchheimer 《Cellular and molecular life sciences : CMLS》1980,36(12):1350-1351
Summary The antileprosy drug dapsone is unable to penetrate intactMycobacterium leprae in vitro, as determined by its effect on o-diphenoloxidase in the bacilli. When combined with the peptide polylysine, the sulfone drug passes through the bacterial cell membranes, and penetrates the enzyme protein, resulting in a 100% inhibition of its activity. 相似文献
87.
88.
89.
A new class of angiotensin-converting enzyme inhibitors 总被引:22,自引:0,他引:22
A A Patchett E Harris E W Tristram M J Wyvratt M T Wu D Taub E R Peterson T J Ikeler J ten Broeke L G Payne D L Ondeyka E D Thorsett W J Greenlee N S Lohr R D Hoffsommer H Joshua W V Ruyle J W Rothrock S D Aster A L Maycock F M Robinson R Hirschmann C S Sweet E H Ulm D M Gross T C Vassil C A Stone 《Nature》1980,288(5788):280-283
Much current attention focuses on the renin-angiotensin system in relation to mechanisms controlling blood pressure and renal function. Recent demonstrations (ref. 1, ref. 2 and refs therein) that angiotensin-converting enzyme inhibitors show promising clinical antihypertensive properties have been of particular interest. We now report on the design of a novel series of substituted N-carboxymethyl-dipeptides which are active in inhibiting angiotensin-converting enzyme at nanomolar levels. We suggest that these compounds are transition-state inhibitors and that extensions of this design to other metalloendopeptidases merit further study. 相似文献
90.
The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth 总被引:1,自引:0,他引:1
Christofk HR Vander Heiden MG Harris MH Ramanathan A Gerszten RE Wei R Fleming MD Schreiber SL Cantley LC 《Nature》2008,452(7184):230-233
Many tumour cells have elevated rates of glucose uptake but reduced rates of oxidative phosphorylation. This persistence of high lactate production by tumours in the presence of oxygen, known as aerobic glycolysis, was first noted by Otto Warburg more than 75 yr ago. How tumour cells establish this altered metabolic phenotype and whether it is essential for tumorigenesis is as yet unknown. Here we show that a single switch in a splice isoform of the glycolytic enzyme pyruvate kinase is necessary for the shift in cellular metabolism to aerobic glycolysis and that this promotes tumorigenesis. Tumour cells have been shown to express exclusively the embryonic M2 isoform of pyruvate kinase. Here we use short hairpin RNA to knockdown pyruvate kinase M2 expression in human cancer cell lines and replace it with pyruvate kinase M1. Switching pyruvate kinase expression to the M1 (adult) isoform leads to reversal of the Warburg effect, as judged by reduced lactate production and increased oxygen consumption, and this correlates with a reduced ability to form tumours in nude mouse xenografts. These results demonstrate that M2 expression is necessary for aerobic glycolysis and that this metabolic phenotype provides a selective growth advantage for tumour cells in vivo. 相似文献