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141.
Hilpert K Elliott MR Volkmer-Engert R Henklein P Donini O Zhou Q Winkler DF Hancock RE 《Chemistry & biology》2006,13(10):1101-1107
Short antimicrobial host-defense peptides represent a possible alternative as lead structures to fight antibiotic resistant bacterial infections. Bac2A is a 12-mer linear variant of the naturally occurring bovine host defense peptide, bactenecin, and demonstrates moderate, broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria as well as against the yeast Candida albicans. With the assistance of a method involving peptide synthesis on a cellulose support, the primary sequence requirements for antimicrobial activity against the human pathogen Pseudomonas aeruginosa of 277 Bac2A variants were investigated by using a luciferase-based assay. Sequence scrambling of Bac2A led to activities ranging from superior or equivalent to Bac2A to inactive, indicating that good activity was not solely dependent on the composition of amino acids or the overall charge or hydrophobicity, but rather required particular linear sequence patterns. A QSAR computational analysis was applied to analyze the data resulting in a model that supported this sequence pattern hypothesis. The activity of selected peptides was confirmed by conventional minimal inhibitory concentration (MIC) analyses with a panel of human pathogen bacteria and fungi. Circular-dichroism (CD) spectroscopy with selected peptides in liposomes and membrane depolarization assays were consistent with a relationship between structure and activity. An additional optimization process was performed involving systematic amino acid substitutions of one of the optimal scrambled peptide variants, resulting in superior active peptide variants. This process provides a cost and time effective enrichment of new candidates for drug development, increasing the chances of finding pharmacologically relevant peptides. 相似文献
142.
The use of redox magnetohydrodynamics (MHD) to enhance the anodic stripping voltammetry (ASV) response of heavy metals has been investigated, with respect to achieving portability: disposable electrodes consisting of screen-printed carbon (SPC) on a low temperature co-fired ceramic (LTCC) substrate, small volumes, and permanent magnets. The analytes tested (Cd(2+), Cu(2+), and Pb(2+)) were codeposited on SPC with Hg(2+) to form a Hg thin film electrode. High concentrations of Fe(3+) were used to produce a high cathodic current which generates a significant Lorentz force in the presence of a magnetic field. This Lorentz force induces solution convection during the deposition step, enhancing the mass transport of analytes to the electrode and increasing their preconcentrated quantity in the mercury thin film. Therefore, larger ASV peaks and improved sensitivities are obtained, compared to analyses performed without a magnet. The effects on ASV signal of varying Hg(2+) concentration (0.10 and 1.0 mM), deposition time (10-600 s), and electrode surface roughness were investigated. In addition, analyses were performed using a real lake water matrix. By using the disposable LTCC-SPC working electrodes in small volumes (150 microL) and with small permanent magnets (0.78 T), peak areas were increased by 75% when compared to the signal obtained in the absence of a magnetic field. A limit of detection of 25 nM for Cd(2+) was observed with only a 1 min preconcentration time. 相似文献
143.
Graether SP DeVries JS McDonald R Rakovszky ML Sykes BD 《Journal of magnetic resonance (San Diego, Calif. : 1997)》2006,178(1):65-71
We show that it is feasible to use a minicoil for solid-state 19F 1H NMR experiments that has short pulse widths, good RF homogeneity, and excellent signal-to-noise for small samples while using low power amplifiers typical to liquid-state NMR. The closely spaced resonant frequencies of 1H and 19F and the ubiquitous use of fluorine in modern plastics and electronic components present two major challenges in the design of a high-sensitivity, high-field 1H/19F probe. Through the selection of specific components, circuit design, and pulse sequence, we were able to build a probe that has low 19F background and excellent separation of 1H and 19F signals. We determine the principle components of the chemical shift anisotropy tensor of 5-fluoroindole-3-acetic acid (5FIAA) and 5-fluorotryptophan. We also solve the crystal structure of 5FIAA, determine the orientation dependence of the chemical shift of a single crystal of 5FIAA, and predict the 19F chemical shift based on the orientation of the fluorine in the crystal. The results show that this 1H/19F probe is suitable for solid-state NMR experiments with low amounts of biological molecules that have been labeled with 19F. 相似文献
144.
Shock waves induced in a volume with a lateral dimension of the order of micrometers are investigated. In particular, shocks of spherical geometry are generated by means of weakly ionized laser produced plasmas. The plasmas are generated by intense pulsed laser radiation focused directly in atmospheric air. These measurements serve as tests for subsequent shocks launched from such laser plasmas into a narrow tube. The shock velocity as well as the density distribution are measured with a laser interferometer. Experimental results for shocks from nanosecond and femtosecond laser-generated plasmas are compared. 相似文献
145.
146.
Shock wave emission induced by intense laser pulses is investigated experimentally. The present work focuses on the conditions of shock wave emission in glycerine and distilled water during the first bubble collapse. Experimental investigations are carried out in liquids as a function of temperature and viscosity. Comparison is made with the theoretical work of Poritsky (Proc 1st US Natl Congress Appl Mech 813–821, 1952) and Brennen (Cavitation and bubble dynamics, Oxford University Press 1995). To the best knowledge of the authors, this is the first experimental verification of those theories. 相似文献
147.
Pulfer MK Harrison K Murphy RC 《Journal of the American Society for Mass Spectrometry》2004,15(2):194-202
Cholesterol is the most abundant neutral lipid in the epithelial lining fluid of the lower airways of the lung also known as pulmonary surfactant and a potential target for reaction with ambient ozone when inspired into the human lung. The isolated double bond of cholesterol has been shown to be susceptible to attack by ozone, but the major reaction product from cholesterol ozonolysis had been remarkably difficult to structurally characterize. Recently, NMR and X-ray crystallography have been used to suggest the formation of a hydroperoxy, hydroxy hemiacetal product, using various derivatives and models of cholesterol to stabilize this chemically reactive product. Electrospray ionization mass spectrometry was used to study the somewhat unstable ozonolysis product of cholesterol which was found to display unique ionization and fragmentation properties when collisionally activated. The electron-deficient carbon atoms of this highly oxygenated product permitted covalent attachment of an acetate anion during negative ion electrospray ionization, leading to the formation of abundant adduct ions at m/z 511. Surprisingly, positive ions were not readily formed. Collision induced dissociation of the adduct anion yielded a major ion at m/z 477, corresponding to the loss of hydrogen peroxide. The most abundant fragment ion following collisional activation was observed at m/z 93, resulting from a complex rearrangement subsequent to the attack of the hydroperoxide anion on the carbon center of the acetate adduct. Based on the interpretation of the tandem mass spectral data, the major cholesterol ozonization product was characterized as a hydroperoxy, hydroxy hemiacetal derivative, which was consistent with the NMR and X-ray crystallographic studies which were carried out on the more stable methyl ether derivative. 相似文献
148.
Kimmel KL Weaver JD Lee M Ellman JA 《Journal of the American Chemical Society》2012,134(22):9058-9061
The highly enantioselective protonation of nitronates formed upon the addition of α-substituted Meldrum's acids to terminally unsubstituted nitroalkenes is described. This work represents the first enantioselective catalytic addition of any type of nucleophile to this class of nitroalkenes. Moreover, for the successful implementation of this method, a new type of N-sulfinyl urea catalyst with chirality residing only at the sulfinyl group was developed, thereby enabling the incorporation of a diverse range of achiral diamine motifs. Finally, the Meldrum's acid addition products were readily converted to pharmaceutically relevant 3,5-disubstituted pyrrolidinones in high yield. 相似文献
149.
Seitchik JL Peeler JC Taylor MT Blackman ML Rhoads TW Cooley RB Refakis C Fox JM Mehl RA 《Journal of the American Chemical Society》2012,134(6):2898-2901
Bioorthogonal ligation methods with improved reaction rates and less obtrusive components are needed for site-specifically labeling proteins without catalysts. Currently no general method exists for in vivo site-specific labeling of proteins that combines fast reaction rate with stable, nontoxic, and chemoselective reagents. To overcome these limitations, we have developed a tetrazine-containing amino acid, 1, that is stable inside living cells. We have site-specifically genetically encoded this unique amino acid in response to an amber codon allowing a single 1 to be placed at any location in a protein. We have demonstrated that protein containing 1 can be ligated to a conformationally strained trans-cyclooctene in vitro and in vivo with reaction rates significantly faster than most commonly used labeling methods. 相似文献
150.
Chan J Lewis AR Indurugalla D Schur M Wakarchuk W Bennet AJ 《Journal of the American Chemical Society》2012,134(8):3748-3757
A series of isotopically labeled natural substrate analogues (phenyl 5-N-acetyl-α-d-neuraminyl-(2→3)-β-d-galactopyranosyl-(1→4)-1-thio-β-d-glucopyranoside; Neu5Acα2,3LacβSPh, and the corresponding 2→6 isomer) were prepared chemoenzymatically in order to characterize, by use of multiple kinetic isotope effect (KIE) measurements, the glycosylation transition states for Vibrio cholerae sialidase-catalyzed hydrolysis reactions. The derived KIEs for Neu5Acα2,3LacβSPh for the ring oxygen ((18)V/K), leaving group oxygen ((18)V/K), C3-S deuterium ((D)V/K(S)) and C3-R deuterium ((D)V/K(R)) are 1.029 ± 0.002, 0.983 ± 0.001, 1.034 ± 0.002, and 1.043 ± 0.002, respectively. In addition, the KIEs for Neu5Acα2,6βSPh for C3-S deuterium ((D)V/K(S)) and C3-R deuterium ((D)V/K(R)) are 1.021 ± 0.001 and 1.049 ± 0.001, respectively. The glycosylation transition state structures for both Neu5Acα2,3LacβSPh and Neu5Acα2,6LacβSPh were modeled computationally using the experimental KIE values as goodness of fit criteria. Both transition states are late with largely cleaved glycosidic bonds coupled to pyranosyl ring flattening ((4)H(5) half-chair conformation) with little or no nucleophilic involvement of the enzymatic tyrosine residue. Notably, the transition state for the catalyzed hydrolysis of Neu5Acα2,6βSPh appears to incorporate a lesser degree of general-acid catalysis, relative to the 2,3-isomer. 相似文献