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排序方式: 共有165条查询结果,搜索用时 15 毫秒
31.
Quentin Coquerel Claire Legendre Jacinthe Frangieh Stephan De Waard Jrme Montnach Leos Cmarko Joseph Khoury Charifat Said Hassane Dimitri Brard Benjamin Siegler Ziad Fajloun Harold De Pomyers Kamel Mabrouk Norbert Weiss Daniel Henrion Pascal Richomme Csar Mattei Michel De Waard Anne-Marie Le Ray Christian Legros 《Molecules (Basel, Switzerland)》2022,27(13)
Voltage-gated Na+ (NaV) channels are significant therapeutic targets for the treatment of cardiac and neurological disorders, thus promoting the search for novel NaV channel ligands. With the objective of discovering new blockers of NaV channel ligands, we screened an In-House vegetal alkaloid library using fluorescence cell-based assays. We screened 62 isoquinoline alkaloids (IA) for their ability to decrease the FRET signal of voltage sensor probes (VSP), which were induced by the activation of NaV channels with batrachotoxin (BTX) in GH3b6 cells. This led to the selection of five IA: liriodenine, oxostephanine, thalmiculine, protopine, and bebeerine, inhibiting the BTX-induced VSP signal with micromolar IC50. These five alkaloids were then assayed using the Na+ fluorescent probe ANG-2 and the patch-clamp technique. Only oxostephanine and liriodenine were able to inhibit the BTX-induced ANG-2 signal in HEK293-hNaV1.3 cells. Indeed, liriodenine and oxostephanine decreased the effects of BTX on Na+ currents elicited by the hNaV1.3 channel, suggesting that conformation change induced by BTX binding could induce a bias in fluorescent assays. However, among the five IA selected in the VSP assay, only bebeerine exhibited strong inhibitory effects against Na+ currents elicited by the hNav1.2 and hNav1.6 channels, with IC50 values below 10 µM. So far, bebeerine is the first BBIQ to have been reported to block NaV channels, with promising therapeutical applications. 相似文献
32.
Jason F. Khoury Jiangang He Jonathan E. Pfluger Ido Hadar Mahalingam Balasubramanian Constantinos C. Stoumpos Rui Zu Venkatraman Gopalan Chris Wolverton Mercouri G. Kanatzidis 《Chemical science》2020,11(3):870
Subchalcogenides are uncommon, and their chemical bonding results from an interplay between metal–metal and metal–chalcogenide interactions. Herein, we present Ir6In32S21, a novel semiconducting subchalcogenide compound that crystallizes in a new structure type in the polar P31m space group, with unit cell parameters a = 13.9378(12) Å, c = 8.2316(8) Å, α = β = 90°, γ = 120°. The compound has a large band gap of 1.48(2) eV, and photoemission and Kelvin probe measurements corroborate this semiconducting behavior with a valence band maximum (VBM) of −4.95(5) eV, conduction band minimum of −3.47(5) eV, and a photoresponse shift of the Fermi level by ∼0.2 eV in the presence of white light. X-ray absorption spectroscopy shows absorption edges for In and Ir do not indicate clear oxidation states, suggesting that the numerous coordination environments of Ir6In32S21 make such assignments ambiguous. Electronic structure calculations confirm the semiconducting character with a nearly direct band gap, and electron localization function (ELF) analysis suggests that the origin of the gap is the result of electron transfer from the In atoms to the S 3p and Ir 5d orbitals. DFT calculations indicate that the average hole effective masses near the VBM (1.19me) are substantially smaller than the average electron masses near the CBM (2.51me), an unusual feature for most semiconductors. The crystal and electronic structure of Ir6In32S21, along with spectroscopic data, suggest that it is neither a true intermetallic nor a classical semiconductor, but somewhere in between those two extremes.Subchalcogenides are uncommon, and their chemical bonding results from an interplay between metal–metal and metal–chalcogenide interactions. 相似文献
33.
After treatment with an appropriate base (butyllithium or sodium amide), 2-alkenyltris(2-methoxymethoxyphenyl)phosphonium salts carrying an allyl, crotyl, or prenyl (3-methyl-2-butenyl) side chain condense with saturated or unsaturated aldehydes to give conjugated dienes with Z/E ratios ranging from 90:10 to > 99:1 and averaging 96:4. Owing to steric congestion, yields are only moderate (on average 41%; extremes 10-79%). The nonvolatile tris(2-methoxymethoxyphenyl)phosphine oxide by-product can be readily isolated and reduced to recover the phosphane starting material, or it may be hydrolyzed to the water-soluble tris(2-hydroxyphenyl)phosphine oxide. 相似文献
34.
Baxter PN Khoury RG Lehn JM Baum G Fenske D 《Chemistry (Weinheim an der Bergstrasse, Germany)》2000,6(22):4140-4148
Ligand 3 has been shown to self-assemble under coordination of copper(II) cations in a 1:1 ratio in acetonitrile to give equilibrating mixtures of a [2 x 2] grid-type tetranuclear structure 1 and a hexanuclear achitecture of hexagonal shape 2. The latter was confirmed by determination of the crystal structure which further indicated that 2 contained acetonitrile molecules and hydroxo groups bound to the copper(II) centers, which are therefore five-coordinate. The structures assigned to 1 and 2 were further supported by the spectral (mass, UV/Vis) data. The self-assembly process is strongly dependent on the conditions of the medium. An increase in concentration in acetronitrile increases the relative amount of hexamer 2, which appears to be the favored entity at the highest concentrations that can be reached before precipitation occurs. On the other hand, in nitromethane only the tetranuclear complex 1 was detected by mass spectrometry. Replacement of nitromethane by acetonitrile and vice versa indicated the reversible switching between a solution containing either 1 alone or an equilibrium mixture of 1 and 2, respectively. In conclusion, the system described presents several remarkable features: 1) self-assembly with substrate binding, 2) dynamic combinatorial structure generation, and 3) environment-induced structural switching amounting in effect to a process of adaptive self-assembly. 相似文献
35.
36.
PEG-400 as an efficient reaction medium for the synthesis of 2,4,5-triaryl-1H-imidazoles and 1,2,4,5-tetraaryl-1H-imidazoles 总被引:1,自引:0,他引:1
An efficient protocol for the one-pot multicomponent synthesis of various 2,4,5-triaryl- IH-imidazoles and 1,2,4,5-tetraaryl-1H-imidazoles using PEG-400 as reaction medium is described. This method has the advantages of good yields, less pollution and simple reaction conditions. 相似文献
37.
Peter Benner Grece El Khoury Miloud Sadkane 《Numerical Linear Algebra with Applications》2014,21(5):645-665
A squared Smith type algorithm for solving large‐scale discrete‐time Stein equations is developed. The algorithm uses restarted Krylov spaces to compute approximations of the squared Smith iterations in low‐rank factored form. Fast convergence results when very few iterations of the alternating direction implicit method are applied to the Stein equation beforehand. The convergence of the algorithm is discussed and its performance is demonstrated by several test examples. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
38.
39.
Helical molecular programming: folding of oligopyridine-dicarboxamides into molecular single helices
Berl V Huc I Khoury RG Lehn JM 《Chemistry (Weinheim an der Bergstrasse, Germany)》2001,7(13):2798-2809
Molecular strands composed of alternating 2,6-diaminopyridine and 2,6-pyridinedicarbonyl units have been designed to self-organize into single stranded helical structures upon forming intramolecular hydrogen bonds. Pentameric strands 11, 12, and 14, heptameric strands 1 and 20, and undecameric strand 15 have been synthesized using stepwise convergent strategies. Single helical conformations have been characterized in the solid state by single crystal X-ray diffraction analysis for four of these compounds. Helices from pentameric strands 12 and 14 extend over one turn, and helices from heptameric 20 and undecameric 15 species extend to one and a half and two and a half turns, respectively. Intramolecular hydrogen bonds are responsible for the strong bending of the strands. 1H NMR shifts both in polar and nonpolar organic solvents indicate intramolecular overlap between the peripheral aromatic groups. Thus, helical conformations also predominate in solution. Molecular stochastic dynamic simulations of strand folding starting from a high energy extended linear conformer show a rapid (600 ps at 300 K) conversion into a stable helical conformation. 相似文献
40.
Hu J Liu Y Khemtong C El Khoury JM McAfoos TJ Taschner IS 《Langmuir : the ACS journal of surfaces and colloids》2004,20(12):4933-4938
Photolithographic attachment of functional organic molecules via ester or amide linkages to self-assembled monolayers (SAMs) on gold thin films was achieved by employing a novel photoreactive surface anchor, 7-diazomethylcarbonyl-2,4,9-trithiaadmantane. The photoreactive SAM was prepared by the spontaneous physical adsorption of the photoreactive surface anchor onto gold surfaces. The alpha-diazo ketone moiety of the SAM was found to display the classical Wolff rearrangement reactivity to produce a ketene intermediate on the exposed area. Organic molecules such as alcohols and amines can thus be attached to the gold surfaces selectively by the facile in situ formation of ester or amide linkages. The structure and reactivity of the photoreactive surface anchor were characterized by real-time FT-IR, fluorescence, and polarization modulation infrared reflectance absorption spectroscopy (PM-IRRAS). The Wolff rearrangement reactivity of the SAM suggested that a "surface-isolated" carbonylcarbene may be generated when the SAM was exposed to 255-nm irradiation. 相似文献