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121.
K. Yirak J.M. Foster P. Hartigan B.H. Wilde M.R. Douglas R. Paguio B.E. Blue D. Martinez D. Farley P.A. Rosen A. Frank 《High Energy Density Physics》2013,9(2):251-257
Recent time-series observations of shock waves in stellar jets taken with the Hubble Space Telescope reveal localized bright knots that persist over nearly 15 years. While some of these features represent shock fronts caused by variable velocities in the flow, others appear at the intersection points between distinct bow shocks. Theoretically, when the angle between two intersecting shocks exceeds a certain critical value, a third shock (Mach stem) should form. Because Mach stems form perpendicular to the direction of flow, incoming particles encounter a normal shock instead of an oblique one, which results in brighter emission at this location. To study this phenomenon in a controlled laboratory setting, we have carried out experiments on the Omega laser aimed at understanding the formation, growth, and destruction of Mach stems in the warm dense plasma regime. Our experimental results indicate how the growth rate depends upon included angle, and numerical simulations indicate that it may be possible to stabilize an already-formed Mach stem below the critical angle when certain conditions are satisfied. 相似文献
122.
Chiosis G Timaul MN Lucas B Munster PN Zheng FF Sepp-Lorenzino L Rosen N 《Chemistry & biology》2001,8(3):289-299
BACKGROUND: The Hsp90s contain a conserved pocket that binds ATP/ADP and plays an important role in the regulation of chaperone function. Occupancy of this pocket by several natural products (geldanamycin (GM) and radicicol) alters Hsp90 function and results in the degradation of a subset of proteins (i.e. steroid receptors, Her2, Raf). We have used the structural features of this pocket to design a small molecule inhibitor of Hsp90. RESULTS: The designed small molecule PU3 competes with GM for Hsp90 binding with a relative affinity of 15-20 microM. PU3 induces degradation of proteins, including Her2, in a manner similar to GM. Furthermore, PU3 inhibits the growth of breast cancer cells causing retinoblastoma protein hypophosphorylation, G1 arrest and differentiation. CONCLUSIONS: PU3 is representative of a novel class of synthetic compounds that binds to Hsp90 and inhibits the proliferation of cancer cells. These reagents could provide a new strategy for the treatment of cancers. 相似文献
123.
Rosen SA Gaffney PR Spiess B Gould IR 《Physical chemistry chemical physics : PCCP》2012,14(2):929-936
Protein kinase B (PKB) is a serine/threonine kinase that plays a key role in the phosphoinositide 3-kinase (PI3K) pathway-one of the most frequently activated proliferation pathways in cancer. In this pathway, PKB is recruited to the plasma membrane by direct interaction of its pleckstrin homology (PH) domain with the inositol phosphate head-group of phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P(3)] or phosphatidylinositol 3,4-bisphosphate [PtdIns(3,4)P(2)]. This recruitment is a critical stage in the activation of PKB, whose downstream effectors play important roles in cell survival, proliferation and growth. It is therefore of great interest to understand PKB's mode of binding, as well as its specificity and affinity for different phosphoinositides. We have used a total of 3 μs of molecular dynamics (MD) simulations to better understand the interactions of the PKB PH domain with the inositol phosphate head-groups of phosphoinositides involved in the PI3K pathway. Our computational models successfully mirror PKB's in vivo selectivity for 3-phosphorylated phosphoinositides. Furthermore, the models also help to rationalize unexpected in vitro data in which inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] binds with a relatively high affinity to the PKB PH domain, despite its parent lipid phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] being known not to bind in vivo. With the support of computational simulations, we propose that when not bonded to a phosphatidate tail Ins(1,4,5)P(3) binds in an orientation in which its inositol ring is flipped with respect to the 3-phosphorylated inositol phosphate ligands and its parent lipid. 相似文献
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A parallel stochastic algorithm is presented for solving the linearly constrained concave global minimization problem. The algorithm is a multistart method and makes use of a Bayesian stopping rule to identify the global minimum with high probability. Computational results are presented for more than 200 problems on a Cray X-MP EA/464 supercomputer. 相似文献
126.
Steven M. Rosen 《Foundations of Physics》1988,18(11):1093-1139
This paper addresses a central question of contemporary theoretical physics: Can a unified account be provided for the known forces of nature? The issue is brought into focus by considering the recently revived Kaluza-Klein approach to unification, a program entailing dimensional transformation through cosmogony. First it is demonstrated that, in a certain sence, revitalized Kaluza-Klein theory appears to undermine the intuitive foundations of mathematical physics, but that this implicit consequence has been repressed at a substantial cost. A fundamental reformulation of the Kaluza-Klein strategy is then undertaken, one that casts it within a new intuitive context. This is followed by a provisional application of the suggested approach to the specific problem of cosmological change. The paper concludes by exploring the far-reaching epistemological implications of the “neo-intuitive” proposal set forth. 相似文献
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129.
The global minimization of large-scale concave quadratic problems over a bounded polyhedral set using a parallel branch and bound approach is considered. The objective function consists of both a concave part (nonlinear variables) and a strictly linear part, which are coupled by the linear constraints. These large-scale problems are characterized by having the number of linear variables much greater than the number of nonlinear variables. A linear underestimating function to the concave part of the objective is easily constructed and minimized over the feasible domain to get both upper and lower bounds on the global minimum function value. At each minor iteration of the algorithm, the feasible domain is divided into subregions and linear underestimating problems over each subregion are solved in parallel. Branch and bound techniques can then be used to eliminate parts of the feasible domain from consideration and improve the upper and lower bounds. It is shown that the algorithm guarantees that a solution is obtained to within any specified tolerance in a finite number of steps. Computational results are presented for problems with 25 and 50 nonlinear variables and up to 400 linear variables. These results were obtained on a four processor CRAY2 using both sequential and parallel implementations of the algorithm. The average parallel solution time was approximately 15 seconds for problems with 400 linear variables and a relative tolerance of 0.001. For a relative tolerance of 0.1, the average computation time appears to increase only linearly with the number of linear variables. 相似文献
130.
Allylic alcohol 7, obtained by a synthesis involving stereoselective aldol addition to an unsaturated aldehyde, is transformed by the Ireland variant of the Claisen rearrangement into unsaturated acid 9. Subsequent elaboration of this material gives homoallylic alcohols 13 and 14, which are hydroborated to obtain primarily 3 and 4. It is shown that the hydroboration is intermolecular, rather than intramolecular. 相似文献