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121.
Vassil St. Georgiev Robert A. Mack David J. Walter Lesley A. Radov Jane E. Baer 《Helvetica chimica acta》1987,70(6):1526-1530
The synthesis and antiallergic activity of a series of 4-(arylamino)-2,5-dihydro-2-oxo-N-(trans-2-phenyl-cyclopropyl)furan-3-carboxamides 10 are described. Treatment of N-substituted 2-amino-4,5-dihydro-4-oxofuran-3-carboxylic acids 9 with chlorooxobis(2-oxo-1,3-oxazolidin-3-yl)phosphorus ( 2 ) and an appropriate aromatic amine in the presence of Et3N, resulted in a novel 3(2H)-furanone-→2(5H)-furanone rearrangement that led to the facile preparation of the new amides 10 . The latter exerted a potent antiallergic activity when tested in the dermal vascular permeability and active anaphylaxis assays in rats. The most active compound 10b inhibited the action of serotonin, histamine, and bradykinin by 94, 92, and 100%, respectively, when administered intraperitoneally to rats at doses of 100 mg/kg. The present series of 10 represents a novel class of antiallergic agents. 相似文献
122.
A proficiency testing round was undertaken to assess the performance of laboratories to measure acrylamide in a sample of crispbread. Retail samples of crispbread were ground to a fine powder and after thorough mixing were packed in 40 g units for distribution. Ten samples were selected at random and analyzed in duplicate for acrylamide by liquid chromatography/mass spectrometry (LC/MS). Standard statistical tests showed that the material was homogeneous for the purposes of proficiency testing. Test samples were distributed to 55 laboratories in 16 countries in Europe, North America, Australia, and the Middle East. The results were analyzed by standard proficiency testing statistical procedures, and laboratories were awarded z-scores on the basis of their reported results. Based on a target standard deviation (sigmap value) taken from the Horwitz equation, for a robust mean value of 1.2 mg/kg acrylamide, satisfactory results (z-score within +/- 2 for those between 0.8 and 1.6 mg/kg) were obtained by 86% of the 37 laboratories that returned results. Only 1 laboratory was unsatisfactory and 4 had questionable results. About equal numbers of laboratories used gas chromatography (GC)/MS and LC/MS procedures with about 25% using MS/MS and one using GC with electron capture detection. There was no evident trend in performance or bias in results. GC/MS and LC/MS data were evenly distributed across the population of laboratories reporting results. 相似文献
123.
Elaine A. Ostrander Gordon W. Robinson Stephen T. Isaacs John Tessman Lesley M. Hallick 《Photochemistry and photobiology》1986,44(1):21-29
Abstract— We have investigated the site specificity of furocoumarins by using fluorescent densitometry to examine the frequency of cleavage by the restriction enzyme Bgl I. This enzyme has an 11 base pair (bp) recognition sequence which varies slightly from site to site because it includes a 5 base pair neutral region. Cleavage at all three Bgl I recognition sites in pBR322 was inhibited by the photoaddition of the psoralen derivative 4'-hydroxymethyl-4,5',8-trimethylpsoralen (HMT) which forms both crosslinks and monoad-ducts in a dose-dependent manner. One site, which contains two thymidines in a crosslinkable configuration, was observed to be markedly more sensitive to HMT photoadducts. In contrast Bgl I cleavage at all sites was relatively resistant to the derivative 5-methylisopsoralen (5-MIP), which forms only monoadducts. When HMT-reacted DNA was generated with widely different ratios of monoad-ducts to crosslinks (3% and 40% crosslinks), essentially the same level and pattern of inhibition was observed in both cases. Taken together, the data imply that differences in inhibition seen at the three cutting sites of Bgl I with HMT are attributable to DNA sequence and the role it plays in adduct positioning. 相似文献
124.
Paul K. Baker Lesley L. Howells Stuart G. Fraser Gordon W. Rogers Martin J. Snowden 《Transition Metal Chemistry》1990,15(1):71-74
Summary The seven-coordinate complexes [MI2(CO)3(NCMe)2] (M=Mo or W) react with two equivalents of L(L=py, 4Me-py, 3Cl-py or 3Br-py) or one equivalent of NN {NN=2,2-bipyridine(bipy), 1,10-phenanthroline(phen), 5,6-dimethyl-1, 10-phenanthroline (5,6-Me2-1, 10-phen), 5-Nitro-1, 10-phenanthroline (5-NO2-1, 10-phen) and C6H4(o-NH2)2 (o-diam) (for M=Mo only)} in CH2Cl2 at room temperature to give the substituted products [MI2(CO)3L2] or [MI2(CO)3(NN)] (1–17) in high yield. The compounds [MI2(CO)3(NCMe)2] react with two equivalents of NN (for M=W, NN=bipy; for M=Mo, NN=phen) to give the dicationic salts [M(CO)3(NN)2]2I(18–19). The compounds [MI2(CO)3(NCMe)2] (M=Mo or W) react with two equivalents of 5,6-Me2-1, 10-phen to yield the monocationic dicarbonyl compounds [MI(CO)2(5,6-Me2-phen)2]I (20 and21). The dicationic mixed ligand complexes [M(CO)3(bipy)(5,6-Me2-phen)]2I (22 and23) are prepared by reacting [MI2(CO)3(NCMe)2] with one equivalent of bipy, followed by anin situ reaction with 5,6-Me2-1, 10-phen to afford the products22 and23. The complexes (1–23) described in this paper have been characterised by elemental analysis (C, H and N), i.r. spectroscopy and, in selected cases,1Hn.m.r. spectroscopy. Magnetic susceptibility measurements show the compounds to be diamagnetic. 相似文献
125.
Bedford RB Betham M Caffyn AJ Charmant JP Lewis-Alleyne LC Long PD Polo-Cerón D Prashar S 《Chemical communications (Cambridge, England)》2008,(8):990-992
Simple chlorodiisopropylphosphine adducts of rhodium, either pre-formed or formed in situ, prove to be highly effective catalysts for the ortho-arylation of phenols. 相似文献
126.
Geary EA McCall KL Turner A Murray PR McInnes EJ Jack LA Yellowlees LJ Robertson N 《Dalton transactions (Cambridge, England : 2003)》2008,(28):3701-3708
A series of [Pt(ii)(diimine)(dithiolate)] complexes of general formula [Pt{X,X'-(CO(2)R)(2)-bpy}(mnt)] (where X = 3, 4 or 5; R = H or Et, bpy = 2,2'-bipyridyl and mnt = maleonitriledithiolate), have been spectroscopically, electrochemically and computationally characterised and compared with the precursors [Pt{X,X'-(CO(2)R)(2)-bpy}Cl(2)] and X,X'-(CO(2)R)(2)-bpy. The study includes cyclic voltammetry, in situ EPR spectroelectrochemical studies of fluid solution and frozen solution samples, UV/Vis/NIR spectroelectrochemistry, hyrid DFT and TD-DFT calculations. The effect of changing the position of the bpy substituents from 3,3' to 4,4' and 5,5' is discussed with reference to electronic changes seen within the different members of the family of molecules. The performance of the mnt complexes in dye-sensitised solar cells has been previously described and the superior performance of [Pt{3,3'-(CO(2)R)(2)-bpy}(mnt)] is now explained in terms of decreased electronic delocalisation through twisting of the bipyridyl ligand as supported by the EPR and computational results. 相似文献
127.
Graziano JJ Liu W Perera R Geierstanger BH Lesley SA Schultz PG 《Journal of the American Chemical Society》2008,130(1):176-185
A protein evolution strategy is described by which double-stranded DNA fragments encoding defined Escherichia coli protein secondary structural elements (alpha-helices, beta-strands, and loops) are assembled semirandomly into sequences comprised of as many as 800 amino acid residues. A library of novel polypeptides generated from this system was inserted into an enhanced green fluorescent protein (EGFP) fusion vector. Library members were screened by fluorescence activated cell sorting (FACS) to identify those polypeptides that fold into soluble, stable structures in vivo that comprised a subset of shorter sequences ( approximately 60 to 100 residues) from the semirandom sequence library. Approximately 108 clones were screened by FACS, a set of 1149 high fluorescence colonies were characterized by dPCR, and four soluble clones with varying amounts of secondary structure were identified. One of these is highly homologous to a domain of aspartate racemase from a marine bacterium (Polaromonas sp.) but is not homologous to any E. coli protein sequence. Several other selected polypeptides have no global sequence homology to any known protein but show significant alpha-helical content, limited dispersion in 1D nuclear magnetic resonance spectra, pH sensitive ANS binding and reversible folding into soluble structures. These results demonstrate that this strategy can generate novel polypeptide sequences containing secondary structure. 相似文献
128.
Peter W. Jones Lesley A. Ward 《Transactions of the American Mathematical Society》2000,352(1):311-362
We construct examples showing that the normalized Lebesgue measure of the conical limit set of a uniformly quasiconformal group acting discontinuously on the disc may take any value between zero and one. This is in contrast to the cases of Fuchsian groups acting on the disc, conformal groups acting discontinuously on the ball in dimension three or higher, uniformly quasiconformal groups acting discontinuously on the ball in dimension three or higher, and discrete groups of biholomorphic mappings acting on the ball in several complex dimensions. In these cases the normalized Lebesgue measure is either zero or one.
129.
130.
Dr. Jesus Angulo Sarah A. Goffin Daivik Gandhi Prof. Mark Searcey Dr. Lesley A. Howell 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(17):5858-5862
Inhibitors of the p53‐MDM2 protein–protein interaction are emerging as a new and validated approach to treating cancer. Herein, we describe the synthesis and inhibitory evaluation of a series of isoquinolin‐1‐one analogues, and highlight the utility of an initial growth‐rates saturation‐transfer difference (STD) NMR approach supported by protein–ligand docking to investigate p53‐MDM2 inhibition. The approach is illustrated by the study of compound 1 , providing key insights into the binding mode of this kind of MDM2 ligands and, more importantly, readily unveiling the previously proposed three‐finger pharmacophore requirement for p53‐MDM2 inhibition. 相似文献