全文获取类型
收费全文 | 205篇 |
免费 | 18篇 |
出版年
2022年 | 2篇 |
2021年 | 5篇 |
2019年 | 3篇 |
2018年 | 2篇 |
2017年 | 2篇 |
2016年 | 5篇 |
2015年 | 4篇 |
2014年 | 9篇 |
2013年 | 7篇 |
2012年 | 20篇 |
2011年 | 17篇 |
2010年 | 5篇 |
2009年 | 10篇 |
2008年 | 7篇 |
2007年 | 10篇 |
2006年 | 16篇 |
2005年 | 5篇 |
2004年 | 5篇 |
2003年 | 5篇 |
2002年 | 3篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1993年 | 5篇 |
1992年 | 9篇 |
1991年 | 1篇 |
1990年 | 5篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1975年 | 1篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 2篇 |
排序方式: 共有223条查询结果,搜索用时 78 毫秒
61.
Xiubin Liang Michael B. Butterworth Kathryn W. Peters Raymond A. Frizzell 《Molecular biology of the cell》2010,21(12):2024-2033
Aldosterone-induced increases in apical membrane epithelial sodium channel (ENaC) density and Na transport involve the induction of 14-3-3 protein expression and their association with Nedd4-2, a substrate of serum- and glucocorticoid-induced kinase (SGK1)-mediated phosphorylation. A search for other 14-3-3 binding proteins in aldosterone-treated cortical collecting duct (CCD) cells identified the Rab-GAP, AS160, an Akt/PKB substrate whose phosphorylation contributes to the recruitment of GLUT4 transporters to adipocyte plasma membranes in response to insulin. In CCD epithelia, aldosterone (10 nM, 24 h) increased AS160 protein expression threefold, with a time-course similar to increases in SGK1 expression. In the absence of aldosterone, AS160 overexpression increased total ENaC expression 2.5-fold but did not increase apical membrane ENaC or amiloride-sensitive Na current (Isc). In AS160 overexpressing epithelia, however, aldosterone increased apical ENaC and Isc 2.5-fold relative to aldosterone alone, thus recruiting the accumulated ENaC to the apical membrane. Conversely, AS160 knockdown increased apical membrane ENaC and Isc under basal conditions to ∼80% of aldosterone-stimulated values, attenuating further steroid effects. Aldosterone induced AS160 phosphorylation at five sites, predominantly at the SGK1 sites T568 and S751, and evoked AS160 binding to the steroid-induced 14-3-3 isoforms, β and ε. AS160 mutations at SGK1 phospho-sites blocked its selective interaction with 14-3-3β and ε and suppressed the ability of expressed AS160 to augment aldosterone action. These findings indicate that the Rab protein regulator, AS160, stabilizes ENaC in a regulated intracellular compartment under basal conditions, and that aldosterone/SGK1-dependent AS160 phosphorylation permits ENaC forward trafficking to the apical membrane to augment Na absorption. 相似文献
62.
The focus of this review is the regulated trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) in distal compartments of the protein secretory pathway and the question of how changes in CFTR cellular distribution may impact on the functions of polarized epithelial cells. We summarize data concerning the cellular localization and activity of CFTR and attempt to synthesize often conflicting results from functional studies of regulated endocytosis and exocytosis in CFTR-expressing cells. In some instances, findings that are inconsistent with regulated CFTR trafficking may result from the use of overexpression systems or nonphysiological experimental conditions. Nevertheless, judging from data on other transporters, an appropriate cellular context is necessary to support regulated CFTR trafficking, even in epithelial cells. The discovery that disease mutations can influence CFTR trafficking in distal secretory and recycling compartments provides support for the concept that regulated CFTR recycling contributes to normal epithelial function, including the control of apical CFTR channel density and epithelial protein secretion. Finally, we propose molecular mechanisms for regulated CFTR endocytosis and exocytosis that are based on CFTR interactions with other proteins, particularly those whose primary function is membrane trafficking. These models provide testable hypotheses that may lead to elucidation of CFTR trafficking mechanisms and permit their experimental manipulation in polarized epithelial cells. 相似文献
63.
64.
Jefferies CA Doyle S Brunner C Dunne A Brint E Wietek C Walch E Wirth T O'Neill LA 《The Journal of biological chemistry》2003,278(28):26258-26264
In this study we have identified members of the Toll-like receptor (TLR) family (namely, TLRs 4, 6, 8, and 9) as proteins to which the intracellular protein tyrosine kinase, Bruton's tyrosine kinase (Btk), binds. Detailed analysis of the interaction between Btk and TLR8 demonstrates that the presence of both Box 2 and 3 motifs in the Toll/interleukin-1 receptor domain was required for the interaction. Furthermore, co-immunoprecipitation experiments revealed that Btk can also interact with key proteins involved in TLR4 signal transduction, namely, MyD88, Mal (MyD88 adapter-like protein), and interleukin-1 receptor-associated kinase-1, but not TRAF-6. The ability of Btk to interact with TLR4 and Mal suggests a role for Btk in lipopolysaccharide (LPS) signal transduction. Stimulation of the human monocytic cell line THP-1 with LPS resulted in an increase in the level of tyrosine phosphorylation of Btk (indicative of activation). The autokinase activity of Btk was also stimulated after LPS stimulation. In addition, a dominant negative form of Btk inhibited TLR4-mediated activation of a nuclear factor kappaB (NFkappaB)-dependent reporter gene in HEK293 cells as well as LPS-induced activation of NFkappaB in the astrocytoma cell line U373 and the monocytic cell line RAW264.7. Further investigation revealed that the Btk-specific inhibitor, LFM-A13, inhibited the activation of NFkappaB by LPS in THP-1 cells. Our findings implicate Btk as a Toll/interleukin-1 receptor domain-binding protein that is important for NFkappaB activation by TLR4. 相似文献
65.
66.
Modulation of K+ channels by arachidonic acid in T84 cells. I.Inhibition of the Ca2+-dependent K+ channel 总被引:1,自引:0,他引:1
Devor Daniel C.; Frizzell Raymond A. 《American journal of physiology. Cell physiology》1998,274(1):C138
TheCl secretory response ofcolonic cells to Ca2+-mediatedagonists is transient despite a sustained elevation of intracellular Ca2+. We evaluated the effects ofsecond messengers proposed to limit Ca2+-mediatedCl secretion on thebasolateral membrane,Ca2+-dependentK+ channel(KCa) in colonic secretorycells, T84. Neither protein kinase C (PKC) nor inositoltetrakisphosphate (1,3,4,5 or 3,4,5,6 form) affectedKCa in excised inside-out patches.In contrast, arachidonic acid (AA; 3 µM) potently inhibitedKCa, reducingNPo, the productof number of channels and channel open probability, by 95%. Theapparent inhibition constant for this AA effect was 425 nM. AAinhibited KCa in the presence ofboth indomethacin and nordihydroguaiaretic acid, blockers of thecyclooxygenase and lipoxygenase pathways. In the presence of albumin,the effect of AA on KCa wasreversed. A similar effect of AA was observed onKCa during outside-out recording.We determined also the effect of thecis-unsaturated fatty acid linoleate,the trans-unsaturated fatty acidelaidate, and the saturated fatty acid myristate. At 3 µM, all ofthese fatty acids inhibited KCa,reducing NPo by 72-86%. Finally, the effect of the cytosolic phospholipaseA2 inhibitorarachidonyltrifluoromethyl ketone(AACOCF3) on thecarbachol-induced short-circuit current(Isc) responsewas determined. In the presence ofAACOCF3, the peakcarbachol-inducedIsc response wasincreased ~2.5-fold. Our results suggest that AA generation inducedby Ca2+-mediated agonists maycontribute to the dissociation observed between the rise inintracellular Ca2+ evoked by theseagonists and the associatedCl secretory response. 相似文献
67.
Raymond A. Frizzell Philip L. Smith Evan Vosburgh Michael Field 《The Journal of membrane biology》1979,46(1):27-39
Summary Measurements of the unidirectional influxes of Na and Cl from the mucosal solution into the epithelium (J
me
) of flounder intestine under short-circuit conditions reveal the presence of a coupled NaCl influx process at the brush border membrane which appears to be essential for the absorption of these ions.J
me
Cl
andJ
me
Na
were inhibited by replacing Na or Cl, respectively, in the bathing media with nontransported ions which also reduced the short-circuit current (I
sc) to near-zero values. Addition of furosemide to the mucosal solution alone inhibited theI
sc and reducedJ
me
Cl
andJ
me
Na
under control conditions, but not in the absence of Na or Cl, respectively. The reductions inJ
me
Cl
andJ
me
Na
elicited by ion replacement or furosemide were approximately equal, suggesting that the coupled influx mechanism mediates a one-for-one entry of these ions into the cell from the mucosal solution. Furosemide inhibited Cl absorption by reducing the unidirectional Cl flux from mucosa to serosa, consistent with its inhibition of the influx process. As in other epithelia, coupled NaCl influx is inhibited by cyclic AMP, which accounts for the decrease in Cl absorption elicited by cyclic nucleotides. These results support the notion thattranscellular NaCl transport is a neutral process and that the serosa-negative transepithelial electrical potential difference and preponderance of Cl over Na absorption under short-circuit conditions result from dissimilar permeabilities of the paracellular pathway to Na and Cl. 相似文献
68.
Klaus Turnheim Raymond A. Frizzell Stanley G. Schultz 《The Journal of membrane biology》1978,39(2-3):233-256
Summary Ouabain abolishes the short-circuit current (I
sc
) and decreases the transepithelial conductance (G
t
) of rabbit colon. In contrast, amphotericin B elicits a maximumI
sc
and markedly increasesG
t
. However, inboth instances the amiloride-sensitive Na entry step is completely blocked, presumably due to an increase in cell Na. Conversely, when Na-depleted tissues are suddenly exposed to 140mm Na, the amiloride-sensitiveI
sc
and the amiloride-sensitive component ofG
t
(
a
G
Na
) increase abruptly to their maximum values and the decline to steady-state plateaus with a half time of 6 min; throughout the decline (I
sc/a
G
Na)=E
Na is constant at a value of 95 mV. In the presence of amphotericin B, theI
sc
abruptly rises to the same maximum but does not decline. These findings indicate that in the presence of 140mm Na the conductance of the amiloride-sensitive Na entry step can vary from a maximum value of approximately 1.6 mmhos/cm2 when cell Na is depleted, to zero when cell Na is abnormally elevated (e.g., in the presence of ouabain or amphotericin B). Our findings are consistent with a system in which the pathway responsible for transcellular Na transport parallels another cellular compartment with which it communicates. The Na capacity of the active transport pathway appears to be very small so that this compartment fills rapidly after exposure of Na-depleted cells to 140mm Na, and active transepithelial Na transport is initiated and reaches steady-state levels quickly. The Na capacity of the second compartment is much larger; the Na content of this compartment appears to be responsible for the negative feedback effect on the permeability of the amiloride-sensitive entry step. 相似文献
69.
Raymond A. Frizzell 《The Journal of membrane biology》1977,35(1):175-187
Summary Addition of Ca ionophore, A23187, to the solution bathing the mucosal surface of descending rabbit colon resulted in a reversal of active Cl absorption to active Cl secretion, a twofold increase in short-circuit current and a 40% increase in tissue conductance without affecting the rate of active Na absorption. These alterations in electrolyte transport are quantitatively similar to those previously observed in response to cyclic 3,5-AMP (cAMP) (R.A. Frizzell, M.J. Koch & S.G. Schultz,J. Membrane Biol.
27:297, 1976). When medium Ca concentration was reduced to 10–6
m, the secretory response to A23187 was abolished but the response to cAMP was unaffected. The ionophore did not influence the cAMP levels of colonic mucosa. Addition of cyclic AMP to colonic strips preloaded with45Ca elicited a reversible increase in Ca efflux from the tissue. These results suggest that an increase in intracellular Ca concentration stimulates colonic electrolyte secretion and that the secretory response to cAMP may be due, at least in part, to a release of Ca from intracellular stores. 相似文献
70.