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101.
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Katarina Kosalková Carlos García-Estrada Carlos Barreiro Martha G Flórez Mohammad S Jami Miguel A Paniagua Juan F Martín 《Microbial cell factories》2012,11(1):5
Background
The secretion of heterologous animal proteins in filamentous fungi is usually limited by bottlenecks in the vesicle-mediated secretory pathway. 相似文献103.
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Braga RC Alves VM Fraga CA Barreiro EJ de Oliveira V Andrade CH 《Journal of molecular modeling》2012,18(5):2065-2078
In modern drug discovery process, ADME/Tox properties should be determined as early as possible in the test cascade to allow
a timely assessment of their property profiles. To help medicinal chemists in designing new compounds with improved pharmacokinetics,
the knowledge of the soft spot position or the site of metabolism (SOM) is needed. In silico methods based on docking, molecular
dynamics and quantum chemical calculations can bring us closer to understand drug metabolism and predict drug–drug interactions.
We report herein on a combined methodology to explore the site of metabolism prediction of a new cardioactive drug prototype,
LASSBio-294 (1), using MetaPrint2D to predict the most likely metabolites, combined with structure-based tools using docking, molecular
dynamics and quantum mechanical calculations to predict the binding of the substrate to CYP2C9 enzyme, to estimate the binding
free energy and to study the energy profiles for the oxidation of (1). Additionally, the computational study was correlated with a metabolic fingerprint profiling using LC-MS analysis. The results
obtained using the computational methods gave valuable information about the probable metabolites of (1) (qualitatively) and also about the important interactions of this lead compound with the amino acid residues of the active
site of CYP2C9. Moreover, using a combination of different levels of theory sheds light on the understanding of (1) metabolism by CYP2C9 and its mechanisms. The metabolic fingerprint profiling of (1) has shown that the metabolites founded in highest concentration in different species were metabolites M1, M2 and M3, whereas M8 was found to be a minor metabolite. Therefore, our computational study allowed a qualitative prediction for the metabolism
of (1). The approach presented here has afforded new opportunities to improve metabolite identification strategies, mediated by
not only CYP2C9 but also other CYP450 family enzymes. 相似文献
105.
Endothelial adhesion receptors are recruited to adherent leukocytes by inclusion in preformed tetraspanin nanoplatforms 总被引:7,自引:1,他引:6
Barreiro O Zamai M Yáñez-Mó M Tejera E López-Romero P Monk PN Gratton E Caiolfa VR Sánchez-Madrid F 《The Journal of cell biology》2008,183(3):527-542
VCAM-1 and ICAM-1, receptors for leukocyte integrins, are recruited to cell–cell contact sites on the apical membrane of activated endothelial cells. In this study, we show that this recruitment is independent of ligand engagement, actin cytoskeleton anchorage, and heterodimer formation. Instead, VCAM-1 and ICAM-1 are recruited by inclusion within specialized preformed tetraspanin-enriched microdomains, which act as endothelial adhesive platforms (EAPs). Using advanced analytical fluorescence techniques, we have characterized the diffusion properties at the single-molecule level, nanoscale organization, and specific intradomain molecular interactions of EAPs in living primary endothelial cells. This study provides compelling evidence for the existence of EAPs as physical entities at the plasma membrane, distinct from lipid rafts. Scanning electron microscopy of immunogold-labeled samples treated with a specific tetraspanin-blocking peptide identify nanoclustering of VCAM-1 and ICAM-1 within EAPs as a novel mechanism for supramolecular organization that regulates the leukocyte integrin–binding capacity of both endothelial receptors during extravasation. 相似文献
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Regasini LO Vellosa JC Silva DH Furlan M de Oliveira OM Khalil NM Brunetti IL Young MC Barreiro EJ Bolzani VS 《Phytochemistry》2008,69(8):1739-1744
A myeloperoxidase inhibitory kaempferol derivative, namely pterogynoside (1), was isolated from fruits of Pterogyne nitens, along with six known flavonols, kaempferol, afzelin, kaempferitrin, quercetin, isoquercetrin and rutin. The structures of all compounds were elucidated primarily from 1D and 2D NMR spectroscopic analyses, as well as by high resolution mass spectrometry. All flavonols were screened to identify secondary metabolites as potential myeloperoxidase (MPO) inhibitors, and at concentrations of 0.50–50 nM, quercetin (5), isoquercitrin (6) and rutin (7) exhibited strong inhibitory effects with IC50 values of 1.22 ± 0.01, 3.75 ± 0.02 and 3.60 ± 0.02, respectively. The MPO activity detected for the new derivative 1 was markedly decreased (IC50 10.3 ± 0.03) when compared with known flavonols 5–7, and interestingly increased when tested against ABTS scavenging activity. 相似文献
109.
Role of PARP activity in lung cancer‐induced cachexia: Effects on muscle oxidative stress,proteolysis, anabolic markers,and phenotype 下载免费PDF全文
110.