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21.
Nadja E. Schoemaker Enrico Frigerio Daniela Fraier Jan H. M. Schellens Hilde Rosing Sindy Jansen Jos H. Beijnen 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2001,763(1-2)
A selective HPLC assay is described for the determination of free and total (free plus polymer-bound) camptothecin (CPT) in human plasma after administration of the anti-tumor drug MAG-CPT (polymer bound camptothecin). Total CPT levels were determined after hydrolysis and free CPT was extracted from acidified plasma using Oasis solid-phase extraction material. Extracts were analyzed on a Zorbax SB-C8 analytical column, using a mixture of acetonitrile–25 mM phosphate buffer (pH 4.0) as the eluent. Detection was performed fluorimetrically. Concentrations of polymer-bound CPT were calculated by subtraction of free from total CPT. The lower limits of quantitation of the methods were 100 ng/ml for total and 1.0 ng/ml for free CPT using 50 μl and 250 μl plasma, respectively. Special attention was paid to the stability of the analytes. The presented method was successfully applied in a clinical pharmacokinetic study in our institute. 相似文献
22.
Mario A. Cepeda Jacob JH. Pelling Caitlin L. Evered Hon S. Leong Sashko Damjanovski 《Experimental cell research》2017,350(1):169-183
Membrane-type-1 Matrix Metalloproteinase (MT1-MMP) is a multifunctional protease that regulates ECM degradation, proMMP-2 activation, and varied cellular processes including migration and viability. MT1-MMP is believed to be a central mediator of tumourigenesis whose role is dictated by its functionally distinct protein domains. Both the localization and signal transduction capabilities of MT1-MMP are dependent on its cytoplasmic domain, exemplifying diverse regulatory functions. To further our understanding of the multifunctional contributions of MT1-MMP to cellular processes, we overexpressed cytoplasmic domain altered constructs in MCF-7 breast cancer cells and analyzed migration and viability in 2D culture conditions, morphology in 3D Matrigel culture, and tumorigenic ability in vivo. We found that the cytoplasmic domain was not needed for MT1-MMP mediated migration promotion, but was necessary to maintain viability during serum depravation in 2D culture. Similarly, during 3D Matrigel culture the cytoplasmic domain of MT1-MMP was not needed to initiate a protrusive phenotype, but was necessary to prevent colony blebbing when cells were serum deprived. We also tested in vivo tumorigenic potential to show that cells expressing cytoplasmic domain altered constructs demonstrated a reduced ability to vascularize tumours. These results suggest that the cytoplasmic domain regulates MT1-MMP function in a manner required for cell survival, but is dispensable for cell migration. 相似文献
23.
Elke EM Brouwers Alwin DR Huitema Jos H Beijnen Jan HM Schellens 《BMC clinical pharmacology》2008,8(1):7
Background
The aim of this study was to evaluate long-term platinum retention in patients treated with cisplatin and oxaliplatin. 相似文献24.
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Jeroen Siebring Matthijs JH Elema Fátima Drubi Vega ákos T Kovács Patsy Haccou Oscar P Kuipers 《The ISME journal》2014,8(1):77-87
Bacillus subtilis sporulation is a last-resort phenotypical adaptation in response to starvation. The regulatory network underlying this developmental pathway has been studied extensively. However, how sporulation initiation is concerted in relation to the environmental nutrient availability is poorly understood. In a fed-batch fermentation set-up, in which sporulation of ultraviolet (UV)-mutagenized B. subtilis is repeatedly triggered by periods of starvation, fitter strains with mutated tagE evolved. These mutants display altered timing of phenotypical differentiation. The substrate for the wall teichoic acid (WTA)-modifying enzyme TagE, UDP-glucose, has recently been shown to be an intracellular proxy for nutrient availability, and influences the timing of cell division. Here we suggest that UDP-glucose also influences timing of cellular differentiation. 相似文献
27.
An intriguing recent study examines the role of miR-1202, a glutamate receptor regulating microRNA, in regulating major depressive disorder. 相似文献
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Jacques P. M. Schellens Helena Vreeling-Sindelárová Rosier J. M. Van Den Munckhof Wilma M. Frederiks 《The Histochemical journal》1995,27(8):609-614
Summary Glycogen phosphorylase activity has been demonstrated at the ultrastructural level in liver and heart tissue of fasted rats.
Unfixed cryostat sections were incubated by mounting them on a semipermeable membrane stretched over a gelled incubation medium.
The medium contained a high concentration of glucose 1-phosphate which enables indirect detection of glycogen phosphorylase
activity on the basis of the synthesis of glycogen. Tissue fixation, dehydration and embedding for electron microscopical
study were performed after the incubation had been completed.
The ultrastructure of both liver and heart tissue was rather well preserved. Glycogen granules resulting from glycogen phosphorylase
activity were found in the cytoplasmic matrix of both hepatocytes and cardiomyocytes; no relationship with membranous structures
could be detected. It is concluded that the semipermeable membrane method is well suited for localizing cytosolic enzyme activities
at the ultrastructural level without prior tissue fixation; this opens further perspectives for correlations between histochemical
and biochemical data. 相似文献
30.
Higher‐order assemblies of oligomeric cargo receptor complexes form the membrane scaffold of the Cvt vesicle 下载免费PDF全文
Arjen J Jakobi Abul K Tarafder Yury S Bykov Andrea Picco Wanda Kukulski Jan Kosinski Wim JH Hagen Arvind C Ravichandran Matthias Wilmanns Marko Kaksonen John AG Briggs Carsten Sachse 《EMBO reports》2016,17(7):1044-1060
Selective autophagy is the mechanism by which large cargos are specifically sequestered for degradation. The structural details of cargo and receptor assembly giving rise to autophagic vesicles remain to be elucidated. We utilize the yeast cytoplasm‐to‐vacuole targeting (Cvt) pathway, a prototype of selective autophagy, together with a multi‐scale analysis approach to study the molecular structure of Cvt vesicles. We report the oligomeric nature of the major Cvt cargo Ape1 with a combined 2.8 Å X‐ray and negative stain EM structure, as well as the secondary cargo Ams1 with a 6.3 Å cryo‐EM structure. We show that the major dodecameric cargo prApe1 exhibits a tendency to form higher‐order chain structures that are broken upon interaction with the receptor Atg19 in vitro. The stoichiometry of these cargo–receptor complexes is key to maintaining the size of the Cvt aggregate in vivo. Using correlative light and electron microscopy, we further visualize key stages of Cvt vesicle biogenesis. Our findings suggest that Atg19 interaction limits Ape1 aggregate size while serving as a vehicle for vacuolar delivery of tetrameric Ams1. 相似文献