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101.
Bateman KP Trimble L Chauret N Silva J Day S Macdonald D Dube D Gallant M Mastracchio A Perrier H Girard Y Nicoll-Griffith D 《Journal of mass spectrometry : JMS》2006,41(6):771-780
L-454,560 is a potent phosphodiesterase 4 (PDE4) inhibitor which was identified as a development candidate for the treatment of asthma and chronic obstructive pulmonary disease (COPD). As part of the discovery of this compound, interspecies in vitro metabolism data was generated using liver microsomes and hepatocytes in order to understand the metabolic fate of the compound. In microsomes, metabolism of the 3-methyl-1,2,4-oxadiazole ring was the predominant pathway observed, including ring cleavage. In rat hepatocytes, hydroxylation of the methyl group on the oxadiazole ring and double-bond isomerization were the most abundant metabolites observed. No major species differences were found in terms of microsomal metabolite profiles. The use of LC with UV and MS detection is highlighted, as well as information from tandem mass spectrometry and NMR. 相似文献
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Shaofeng Duan Shuang Cai Yumei Xie Taryn Bagby Shenqiang Ren M. Laird Forrest 《Journal of polymer science. Part A, Polymer chemistry》2012,50(13):2715-2724
Functionalized polymeric nanocarriers have been recognized as drug delivery platforms for delivering therapeutic concentrations of chemotherapies. Of this category, star‐shaped multiarm polymers are emerging candidates for targeted delivery of anticancer drugs, due to their compact structure, narrow size distribution, large surface area, and high water solubility. In this study, we synthesized a multiarm poly(acrylic acid) star polymer via macromolecular design via the interchange (MADIX)/reversible addition fragmentation chain transfer (MADIX/RAFT) polymerization and characterized it using nuclear magnetic resonance (NMR) and size exclusion chromatography. The poly(acrylic acid) star polymer demonstrated excellent water solubility and extremely low viscosity, making it highly suited for targeted drug delivery. Subsequently, we selected a hydrophilic drug, cisplatin, and a hydrophobic nitric oxide (NO)‐donating prodrug, O2‐(2,4‐dinitrophenyl) 1‐[4‐(2‐hydroxy)ethyl]‐3‐methylpiperazin‐1‐yl]diazen‐1‐ium‐1,2‐diolate, as two model compounds to evaluate the feasibility of using poly(acrylic acid) star polymers for the delivery of chemotherapeutics. After synthesizing and characterizing two poly(acrylic acid) star polymer‐based nanoconjugates, poly(acrylic acid)–cisplatin (acid–Pt) and poly(acrylic acid–NO (acid–NO) prodrug, the in vitro drug release kinetics of both the acid–Pt and the acid–NO were determined at physiological conditions. In summary, we have designed and evaluated a polymeric nanocarrier for sustained‐delivery of chemotherapies, either as a single treatment or a combination therapy regimen. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012 相似文献
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Aguilar-Arevalo AA Bazarko AO Brice SJ Brown BC Bugel L Cao J Coney L Conrad JM Cox DC Curioni A Djurcic Z Finley DA Fleming BT Ford R Garcia FG Garvey GT Green C Green JA Hart TL Hawker E Imlay R Johnson RA Kasper P Katori T Kobilarcik T Kourbanis I Koutsoliotas S Laird EM Link JM Liu Y Liu Y Louis WC Mahn KB Marsh W Martin PS McGregor G Metcalf W Meyers PD Mills F Mills GB Monroe J Moore CD Nelson RH Nienaber P Ouedraogo S Patterson RB Perevalov D Polly CC Prebys E Raaf JL Ray H Roe BP 《Physical review letters》2007,98(23):231801
The MiniBooNE Collaboration reports first results of a search for nu e appearance in a nu mu beam. With two largely independent analyses, we observe no significant excess of events above the background for reconstructed neutrino energies above 475 MeV. The data are consistent with no oscillations within a two-neutrino appearance-only oscillation model. 相似文献
106.
Time-dependent fluorescence (TDF) of a chromophore in a polar or nonpolar solvent is frequently simulated using linear-response approximations. It is shown that one such linear-response-type approximation for the TDF Stokes shift derived by Carter and Hynes [J. Chem. Phys. 94, 5961 (1991)] that is based on excited-state dynamics gives the same result as that obtained by assuming Gaussian statistics for the energy gap. The derivation provides insight into the much discussed relationship between linear response and Gaussian statistics. In particular, subtle but important differences between the two approximations are illuminated that suggest that the result is likely more generally applicable than suggested by the usual linearization procedure. In addition, the assumption of Gaussian statistics directly points to straightforward checks of the validity of the approximation with essentially no additional computational effort. 相似文献
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Olivier Mozziconacci Jordan T. Stobaugh Rupesh Bommana Joshua Woods Edward Franklin James W. Jorgenson M. Laird Forrest Christian Schöneich John F. Stobaugh 《Chromatographia》2017,80(9):1299-1318
In recent years, protein therapeutics have seen increasing use in the therapeutic arena. As with traditional small molecule drug substances, one is obligated to ensure purity and stability of the various dosage forms. With these higher molecular weight therapeutics, a common approach for analytical characterization is enzymatic digestion followed by gradient elution liquid chromatography with mass spectrometry detection to create a peptide map (bottom-up protein analysis). Due to the difficulty to separate mixtures frequently encountered, there is the need for advanced chromatographic systems featuring increased resolution and/or peak capacity that can be operated in the gradient elution format. Presently, we describe an extreme ultra-pressure liquid chromatography (XUPLC) system that has been implemented as an in-house add-on to a commercial ultra-pressure chromatography system. This add-on allows operation at the 38 Kpsi range, accommodates the use of capillary columns in excess of 1 m packed with sub-2-µm particles and can be operated in the gradient elution format. To evaluate the utility of this system, rat growth hormone was used as a model protein and was exposed to light (λ 254 nm) to create a stress environment. When enzymatic digests of control and stressed protein were analyzed with the XUPLC system using MS detection, greater than 92% peptide coverage was achieved, including the identification some peptides where pre-oxidation of Met residues had occurred, as well as chemistry specifically related to the photolysis of protein disulfide linkages. When the same samples were analyzed by commercial UPLC and compared to the XUPLC results, the utility of the increased peak capacity available with the XUPLC was apparent as previously co-eluting peaks were now well resolved. In particular, one specific degradation route was identified where a pair of isobaric cis/trans diastereomerically related peptides were well resolved by XUPLC while they were unresolved by UPLC. Clearly the use of this system operating at a higher pressure regime with long capillary columns is and will be useful in continued investigations of protein stability, especially in cases where only subtle differences in the amino acid residues have occurred during degradation. 相似文献
108.
Simon Anna Fallis Jennifer Spyrou Artemis Laird Alison M. Ruiz Chris Buchmann Lothar Fulton Brian R. Hutcheon Dave Martin Lars Ottewell Dave Rojas Alex 《The European Physical Journal A - Hadrons and Nuclei》2013,49(5):1-5
The European Physical Journal A - Although glueballs, as one of the type of exotic hadrons allowed by QCD, have been well established on the lattice, experimental searches up to this date for bound... 相似文献
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