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1.
Femke M van de Water Johanna M Boleij Janny G P Peters Frans G M Russel Rosalinde Masereeuw 《European journal of pharmaceutical sciences》2007,30(1):36-44
The activity of P-glycoprotein (Pgp/MDR1/ABCB1) and multidrug resistance proteins (MRP/ABCC) influence the pharmacokinetics and bioavailability of many drugs. Few suitable cell lines for the study of drug transport exist. Additional non-human cell lines may help clarify species differences and contribute to the current knowledge of drug transport. The aim of the present study was to characterize three rat epithelial cell lines for transporter expression and activity. Transporter expression was assessed in intestinal IEC-6 and renal GERP and NRK-52E cells using RT-PCR and Western blot analysis. Pgp and Mrp transport activity were analyzed by measuring calcein accumulation and glutathione-S-bimane efflux, respectively. The three cell lines showed Pgp expression and Pgp-dependent transport, both decreasing with culture time after reaching confluency. Besides Pgp, cells expressed Mrp1, Mrp3, Mrp4, and Mrp5, while Mrp2 and Mrp6 were absent. In addition, they showed temperature- and Mrp-dependent efflux of glutathione-S-bimane. Exposure to a panel of different inhibitors showed that this efflux was probably mediated by Mrp4. In conclusion, the three rat epithelial cell lines investigated showed Pgp and Mrp expression and transport. Mrp dependent transport was most likely mediated by Mrp4. In future, these cell lines may be used as in vitro models to study drug transport. 相似文献
2.
Long-term maintenance of hematopoietic stem cells does not require contact with embryo-derived stromal cells in cocultures 总被引:5,自引:0,他引:5
Oostendorp RA Robin C Steinhoff C Marz S Bräuer R Nuber UA Dzierzak EA Peschel C 《Stem cells (Dayton, Ohio)》2005,23(6):842-851
We recently established that two midgestation-derived stromal clones--UG26-1B6, urogenital ridge-derived, and EL08-1D2, embryonic liver-derived--support the maintenance of murine adult bone marrow and human cord blood hematopoietic repopulating stem cells (HSCs). In this study, we investigate whether direct HSC-stroma contact is required for this stem cell maintenance. Adult bone marrow ckit+ Ly-6C- side population (K6-SP) cells and stromal cells were cocultured under contact or noncontact conditions. These experiments showed that HSCs were maintained for at least 4 weeks in culture and that direct contact between HSCs and stromal cells was not required. To find out which factors might be involved in HSC maintenance, we compared the gene expression profile of EL08-1D2 and UG26-1B6 with four HSC-nonsupportive clones. We found that EL08-1D2 and UG26-1B6 both expressed 21 genes at a higher level, including the putative secreted factors fibroblast growth factor-7, insulin-like growth factor-binding proteins 3 and 4, pleiotrophin, pentaxin-related, and thrombospondin 2, whereas 11 genes, including GPX-3 and HSP27, were expressed at a lower level. In summary, we show for the first time long-term maintenance of adult bone marrow HSCs in stroma noncontact cultures and identify some secreted molecules that may be involved in this support. 相似文献
3.
Chiara Favero Laura Giordano Silvia Maria Mihaila Rosalinde Masereeuw Alberto Ortiz Maria Dolores Sanchez-Nio 《Toxins》2022,14(9)
Chronic kidney disease (CKD) is projected to become the fifth global cause of death by 2040 as a result of key shortcomings in the current methods available to diagnose and treat kidney diseases. In this regard, the novel holobiont concept, used to describe an individual host and its microbial community, may pave the way towards a better understanding of kidney disease pathogenesis and progression. Microbiota-modulating or -derived interventions include probiotics, prebiotics, synbiotics and postbiotics. As of 2019, the concept of postbiotics was updated by the International Scientific Association of Probiotics and Prebiotics (ISAPP) to refer to preparations of inanimate microorganisms and/or their components that confer a health benefit to the host. By explicitly excluding purified metabolites without a cellular biomass, any literature making use of such term is potentially rendered obsolete. We now review the revised concept of postbiotics concerning their potential clinical applications and research in kidney disease, by discussing in detail several formulations that are undergoing preclinical development such as GABA-salt for diet-induced hypertension and kidney injury, sonicated Lactobacillus paracasei in high fat diet-induced kidney injury, GABA-salt, lacto-GABA-salt and postbiotic-GABA-salt in acute kidney injury, and O. formigenes lysates for hyperoxaluria. Furthermore, we provide a roadmap for postbiotics research in kidney disease to expedite clinical translation. 相似文献
4.
Kalsbeek A Buijs RM van Schaik R Kaptein E Visser TJ Doulabi BZ Fliers E 《Endocrinology》2005,146(3):1418-1427
Type II deiodinase (D2) plays a key role in regulating thyroid hormone-dependent processes in, among others, the central nervous system (CNS) by accelerating the intracellular conversion of T4 into active T3. Just like the well-known daily rhythm of the hormones of the hypothalamo-pituitary-thyroid axis, D2 activity also appears to show daily variations. However, the mechanisms involved in generating these daily variations, especially in the CNS, are not known. Therefore, we decided to investigate the role the master biological clock, located in the hypothalamus, plays with respect to D2 activity in the rat CNS as well as the role of one of its main hormonal outputs, i.e. plasma corticosterone. D2 activity showed a significant daily rhythm in the pineal and pituitary gland as well as hypothalamic and cortical brain tissue, albeit with a different timing of its acrophase in the different tissues. Ablation of the biological clock abolished the daily variations of D2 activity in all four tissues studied. The main effect of the knockout of the suprachiasmatic nuclei (SCN) was a reduction of nocturnal peak levels in D2 activity. Moreover, contrary to previous observations in SCN-intact animals, in SCN-lesioned animals, the decreased levels of D2 activity are accompanied by decreased plasma levels of the thyroid hormones, suggesting that the SCN separately stimulates D2 activity as well as the hypothalamo-pituitary-thyroid axis. 相似文献
5.
New insights into the effects of biomaterial chemistry and topography on the morphology of kidney epithelial cells 下载免费PDF全文
Frits Hulshof Carolien Schophuizen Milos Mihajlovic Clemens van Blitterswijk Rosalinde Masereeuw Jan de Boer Dimitrios Stamatialis 《Journal of tissue engineering and regenerative medicine》2018,12(2):e817-e827
Increasing incidence of renal pathology in the western world calls for innovative research for the development of cell‐based therapies such as a bioartificial kidney (BAK) device. To fulfil the multitude of kidney functions, the core component of the BAK is a living membrane consisting of a tight kidney cell monolayer with preserved functional organic ion transporters cultured on a polymeric membrane surface. This membrane, on one side, is in contact with blood and therefore should have excellent blood compatibility, whereas the other side should facilitate functional monolayer formation. This work investigated the effect of membrane chemistry and surface topography on kidney epithelial cells to improve the formation of a functional monolayer. To achieve this, microtopographies were fabricated with high resolution and reproducibility on polystyrene films and on polyethersulfone‐polyvinyl pyrrolidone (PES‐PVP) porous membranes. A conditionally immortalized proximal tubule epithelial cell line (ciPTEC) was cultured on both, and subsequently, the cell morphology and monolayer formation were assessed. Our results showed that L‐dopamine coating of the PES‐PVP was sufficient to support ciPTEC monolayer formation. The polystyrene topographies with large features were able to align the cells in various patterns without significantly disruption of monolayer formation; however, the PES‐PVP topographies with large features disrupted the monolayer. In contrast, the PES‐PVP membranes with small features and with large spacing supported well the ciPTEC monolayer formation. In addition, the topographical PES‐PVP membranes were compatible as a substrate membrane to measure organic cation transporter activity in Transwell® systems. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
6.
Carolien M. S. Schophuizen Martijn J. Wilmer Jitske Jansen Lena Gustavsson Constanze Hilgendorf Joost G. J. Hoenderop Lambert P. van den Heuvel Rosalinde Masereeuw 《Pflügers Archiv : European journal of physiology》2013,465(12):1701-1714
Several organic cations, such as guanidino compounds and polyamines, have been found to accumulate in plasma of patients with kidney failure due to inadequate renal clearance. Here, we studied the interaction of cationic uremic toxins with renal organic cation transport in a conditionally immortalized human proximal tubule epithelial cell line (ciPTEC). Transporter activity was measured and validated in cell suspensions by studying uptake of the fluorescent substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium-iodide (ASP+). Subsequently, the inhibitory potencies of the cationic uremic toxins, cadaverine, putrescine, spermine and spermidine (polyamines), acrolein (polyamine breakdown product), guanidine, and methylguanidine (guanidino compounds) were determined. Concentration-dependent inhibition of ASP+ uptake by TPA, cimetidine, quinidine, and metformin confirmed functional endogenous organic cation transporter 2 (OCT2) expression in ciPTEC. All uremic toxins tested inhibited ASP+ uptake, of which acrolein required the lowest concentration to provoke a half-maximal inhibition (IC50?=?44?±?2 μM). A Dixon plot was constructed for acrolein using three independent inhibition curves with 10, 20, or 30 μM ASP+, which demonstrated competitive or mixed type of interaction (K i?=?93 ± 16 μM). Exposing the cells to a mixture of cationic uremic toxins resulted in a more potent and biphasic inhibitory response curve, indicating complex interactions between the toxins and ASP+ uptake. In conclusion, ciPTEC proves a suitable model to study cationic xenobiotic interactions. Inhibition of cellular uptake transport was demonstrated for several uremic toxins, which might indicate a possible role in kidney disease progression during uremia. 相似文献
7.
Reza Moghadasali Henricus A.M. Mutsaers Mahnaz Azarnia Nasser Aghdami Hossein Baharvand Ruurd Torensma Martijn J.G. Wilmer Rosalinde Masereeuw 《Experimental and toxicologic pathology》2013,65(5):595-600
Bone marrow-derived mesenchymal stem cells (MSCs) have the capacity to regenerate renal tubule epithelia and repair renal function without fusing with resident tubular cells. The goal of the present project was to investigate the role of MSCs secreted cytokines on tubule cell viability and regeneration after a toxic insult, using a conditionally immortalized human proximal tubule epithelial cell (ciPTEC) line. Gentamicin was used to induce nephrotoxicity, and cell viability and migration were studied in absence and presence of human MSC-conditioned medium (hMSC-CM) i.e. medium containing soluble factors produced and secreted by MSCs. Exposure of ciPTEC to 0–3000 μg/ml gentamicin for 24 h caused a significant dose-dependent increase in cell death. We further demonstrated that the nephrotoxic effect of 2000 μg/ml gentamicin was recovered partially by exposing cells to hMSC-CM. Moreover, exposure of ciPTEC to gentamicin (1500–3000 μg/ml) for 7 days completely attenuated the migratory capacity of the cells. In addition, following scrape-wounding, cell migration of both untreated and gentamicin-exposed cells was increased in the presence of hMSC-CM, as compared to exposures to normal medium, indicating improved cell recovery. Our data suggest that cytokines secreted by MSCs stimulate renal tubule cell regeneration after nephrotoxicity. 相似文献
8.
Mathijssen NC Masereeuw R Verbeek K Lavergne JM Costa JM van Heerde WL Nováková IR 《British journal of haematology》2004,125(4):494-499
Inherited factor VII (FVII) deficiency is a rare autosomal recessive disorder associated with a bleeding tendency. We describe three patients with congenital FVII deficiency who have been treated with activated recombinant factor VII (rVIIa). Two patients had novel mutations and were treated prophylactically with 1.2 mg rVIIa two to three times a week. Patients 1 and 2 had a severe bleeding tendency. The frequency and severity of bleeding decreased by treatment with rVIIa compared with similar treatment with plasma-derived FVII. The third patient with a moderate bleeding phenotype was treated on demand and showed no change in the frequency of bleeding upon treatment with rVIIa or plasma products. The beneficial effect of rVIIa cannot be explained by the rVIIa half-lives. Pharmacokinetical analysis showed rVIIa activity half-lives of 35, 50 and 54 min for patients 1, 2 and 3, respectively. In conclusion, prophylactic treatment of FVII deficient patients with rVIIa appears to be applicable, safe and successful, although the mechanism of action remains to be elucidated. 相似文献
9.
Yvonne M. Drewes MD Rosalinde K. E. Poortvliet MD Jeanet W. Blom MD PhD Wouter de Ruijter MD PhD Rudi G. J. Westendorp MD PhD David J. Stott MD PhD Henk J. Blom PhD Ian Ford PhD Naveed Sattar MD PhD J. Wouter Jukema MD PhD Willem J. J. Assendelft MD PhD Anton J. M. de Craen PhD Jacobijn Gussekloo PhD 《Journal of the American Geriatrics Society》2014,62(2):213-221
10.
Marianne K. Vormann Linda Gijzen Simon Hutter Lisette Boot Arnaud Nicolas Angelique van den Heuvel Jelle Vriend Chee Ping Ng Tom T. G. Nieskens Vincent van Duinen Bjorn de Wagenaar Rosalinde Masereeuw Laura Suter-Dick Sebastiaan J. Trietsch Martijn Wilmer Jos Joore Paul Vulto Henriette L. Lanz 《The AAPS journal》2018,20(5):90
Proximal tubules in the kidney play a crucial role in reabsorbing and eliminating substrates from the body into the urine, leading to high local concentrations of xenobiotics. This makes the proximal tubule a major target for drug toxicity that needs to be evaluated during the drug development process. Here, we describe an advanced in vitro model consisting of fully polarized renal proximal tubular epithelial cells cultured in a microfluidic system. Up to 40 leak-tight tubules were cultured on this platform that provides access to the basolateral as well as the apical side of the epithelial cells. Exposure to the nephrotoxicant cisplatin caused a dose-dependent disruption of the epithelial barrier, a decrease in viability, an increase in effluent LDH activity, and changes in expression of tight-junction marker zona-occludence 1, actin, and DNA-damage marker H2A.X, as detected by immunostaining. Activity and inhibition of the efflux pumps P-glycoprotein (P-gp) and multidrug resistance protein (MRP) were demonstrated using fluorescence-based transporter assays. In addition, the transepithelial transport function from the basolateral to the apical side of the proximal tubule was studied. The apparent permeability of the fluorescent P-gp substrate rhodamine 123 was decreased by 35% by co-incubation with cyclosporin A. Furthermore, the activity of the glucose transporter SGLT2 was demonstrated using the fluorescent glucose analog 6-NBDG which was sensitive to inhibition by phlorizin. Our results demonstrate that we developed a functional 3D perfused proximal tubule model with advanced renal epithelial characteristics that can be used for drug screening studies. 相似文献