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排序方式: 共有102条查询结果,搜索用时 140 毫秒
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Tobias Ruck Stefanie Bock Steffen Pfeuffer Christina B.Schroeter Derya Cengiz Paul Marciniak Maren Lindner Alexander Herrmann Marie Liebmann Stjepana Kovac Lukas Gola Leoni Rolfes Marc Pawlitzki Nils Opel Tim Hahn Udo Dannlowski Thomas Pap Felix Luessi Julian A.Schreiber Bernhard Wünsch Tanja Kuhlmann Guiscard Seebohm Bjrn Tackenberg Patricia Seja Frank Dring Erhard Wischmeyer Achmet Imam Chasan Johannes Roth Luisa Klotz Gerd Meyer zu Hrste Heinz Wiendl Tobias Marschall Stefan Floess Jochen Huehn Thomas Budde Tobias Bopp Stefan Bittner Sven G.Meuth 《Cell research》2022,32(1):72-88
It remains largely unclear how thymocytes translate relative differences in T cell receptor (TCR) signal strength into distinct developmental programs that driv... 相似文献
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Using representative members of each of three homologous series of chemicals-ketones, acetates and alcohols-we measured nasal pungency thresholds in anosmics via two stimulus-delivery systems. The first system consists of the fairly commonly used 270 ml, plastic 'squeeze bottles'. The second system consists of 1900 ml, glass vessels with Teflon tubing and nose-pieces. Although bulkier and more susceptible to mechanical breakage, the glass vessels possess advantages that can allow them to provide 'environmentally realistic' chemosensory thresholds, i.e. thresholds closer in absolute values to those that might be obtained under whole-body exposures. Such advantages include a larger volume of the vapor-source to accommodate whole sniffs, and a tight nose-nose-piece connection to avoid stimulus dilution. The outcome revealed that, for every chemical, the glass vessels provided nasal pungency thresholds significantly lower than those provided by the squeeze bottles. The difference amounted, on average, to a factor of 4.6, though the relative potency of the compounds remained the same under both systems. Additionally, when tested with the highest homologues used here, namely, octyl acetate and 1-octanol, anosmics using the glass vessels had little or no difficulty achieving the criterion for threshold whereas they did have difficulty when using the squeeze bottles. 相似文献
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F Becq Y Mettey M A Gray L J Galietta R L Dormer M Merten T Métayé V Chappe C Marvingt-Mounir O Zegarra-Moran R Tarran L Bulteau R Dérand M M Pereira M A McPherson C Rogier M Joffre B E Argent D Sarrouilhe W Kammouni C Figarella B Verrier M Gola J M Vierfond 《The Journal of biological chemistry》1999,274(39):27415-27425
Chloride channels play an important role in the physiology and pathophysiology of epithelia, but their pharmacology is still poorly developed. We have chemically synthesized a series of substituted benzo[c]quinolizinium (MPB) compounds. Among them, 6-hydroxy-7-chlorobenzo[c]quinolizinium (MPB-27) and 6-hydroxy-10-chlorobenzo[c]quinolizinium (MPB-07), which we show to be potent and selective activators of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. We examined the effect of MPB compounds on the activity of CFTR channels in a variety of established epithelial and nonepithelial cell systems. Using the iodide efflux technique, we show that MPB compounds activate CFTR chloride channels in Chinese hamster ovary (CHO) cells stably expressing CFTR but not in CHO cells lacking CFTR. Single and whole cell patch clamp recordings from CHO cells confirm that CFTR is the only channel activated by the drugs. Ussing chamber experiments reveal that the apical addition of MPB to human nasal epithelial cells produces a large increase of the short circuit current. This current can be totally inhibited by glibenclamide. Whole cell experiments performed on native respiratory cells isolated from wild type and CF null mice also show that MPB compounds specifically activate CFTR channels. The activation of CFTR by MPB compounds was glibenclamide-sensitive and 4, 4'-diisothiocyanostilbene-2,2'-disulfonic acid-insensitive. In the human tracheal gland cell line MM39, MPB drugs activate CFTR channels and stimulate the secretion of the antibacterial secretory leukoproteinase inhibitor. In submandibular acinar cells, MPB compounds slightly stimulate CFTR-mediated submandibular mucin secretion without changing intracellular cAMP and ATP levels. Similarly, in CHO cells MPB compounds have no effect on the intracellular levels of cAMP and ATP or on the activity of various protein phosphatases (PP1, PP2A, PP2C, or alkaline phosphatase). Our results provide evidence that substituted benzo[c]quinolizinium compounds are a novel family of activators of CFTR and of CFTR-mediated protein secretion and therefore represent a new tool to study CFTR-mediated chloride and secretory functions in epithelial tissues. 相似文献
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Mitchel RE Hasu M Bugden M Wyatt H Little MP Gola A Hildebrandt G Priest ND Whitman SC 《Radiation research》2011,175(5):665-676
The hypothesis that single low-dose exposures (0.025-0.5 Gy) to low-LET radiation given at either high (about 150 mGy/min) or low (1 mGy/min) dose rate would promote aortic atherosclerosis was tested in female C57BL/6J mice genetically predisposed to this disease (ApoE?/?). Mice were exposed either at an early stage of disease (2 months of age) and examined 3 or 6 months later or at a late stage of disease (8 months of age) and examined 2 or 4 months later. Changes in aortic lesion frequency, size and severity as well as total serum cholesterol levels and the uptake of lesion lipids by lesion-associated macrophages were assessed. Statistically significant changes in each of these measures were observed, depending on dose, dose rate and disease stage. In all cases, the results were distinctly non-linear with dose, with maximum effects tending to occur at 25 or 50 mGy. In general, low doses given at low dose rate during either early- or late-stage disease were protective, slowing the progression of the disease by one or more of these measures. Most effects appeared and persisted for months after the single exposures, but some were ultimately transitory. In contrast to exposure at low dose rate, high-dose-rate exposure during early-stage disease produced both protective and detrimental effects, suggesting that low doses may influence this disease by more than one mechanism and that dose rate is an important parameter. These results contrast with the known, generally detrimental effects of high doses on the progression of this disease in the same mice and in humans, suggesting that a linear extrapolation of the known increased risk from high doses to low doses is not appropriate. 相似文献
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Julien M Verrier B Cerutti M Chappe V Gola M Devauchelle G Becq F 《The Journal of membrane biology》1999,168(3):229-239
Increasing evidence is now accumulating for the involvement of the cystic fibrosis transmembrane conductance regulator (CFTR)
in the control of the outwardly rectifying chloride channel (ORCC). We have examined the sensitivity of ORCC to the sulfonylurea
drug glibenclamide in Hi-5 (Trichoplusia ni) insect cells infected with recombinant baculovirus expressing either wild-type CFTR, ΔF508-CFTR or E. coliβ galactosidase cDNA and in control cells either infected with virus alone or uninfected. Iodide efflux and single channel
patch-clamp experiments confirmed that forskolin and 1-methyl-3-isobutyl xanthine (IBMX) or 7-methyl-1,3 dipropyl xanthine
(DPMX) activate CFTR channels (unitary conductance: 9.1 ± 1.6 pS) only in cells expressing CFTR. In contrast, we identified
4-acetamido-4′-isothiocyanatostilbene-2,2′-disulfonic acid (SITS)-sensitive ORCC in excised membrane patches in any of the
cells studied, with similar conductance (22 ± 2.5 pS at −80 mV; 55 ± 4.1 pS at +80 mV) and properties. In the presence of
500 μm SITS, channel open probability (P
o
) of ORCC was reversibly reduced to 0.05 ± 0.01 in CFTR-cells, to 0.07 ± 0.02 in non-CFTR expressing cells and to 0.05 ± 0.02
in ΔF508-cells. In Hi-5 cells that did not express CFTR, glibenclamide failed to inhibit ORCC activity even at high concentrations
(100 μm), whereas 500 μm SITS reversibly inhibited ORCC. In contrast in cells expressing CFTR or ΔF508, glibenclamide dose dependently (IC50= 17 μm, Hill coefficient 1.2) and reversibly inhibited ORCC. Cytoplasmic application of 100 μm glibenclamide reversibly reduced P
o
from 0.88 ± 0.03 to 0.09 ± 0.02 (wash: P
o
= 0.85 ± 0.1) in CFTR cells and from 0.89 ± 0.05 to 0.08 ± 0.05 (wash: P
o
= 0.87 ± 0.1) in ΔF508 cells. In non-CFTR expressing cells, glibenclamide (100 μm) was without effect on P
o
(control: P
o
= 0.89 ± 0.09, glib.: P
o
= 0.86 ± 0.02; wash: P
o
= 0.87 ± 0.05). These data strongly suggest that the expression of CFTR confers glibenclamide sensitivity to the ORCC in Hi-5
cells.
Received: 23 October 1998/Revised: 29 December 1998 相似文献
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