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排序方式: 共有101条查询结果,搜索用时 62 毫秒
1.
Substrate and inhibitor specificity of anion exchangers on the brush border membrane of rabbit ileum
Roy G. Knickelbein Peter S. Aronson John W. Dobbins 《The Journal of membrane biology》1985,88(2):199-204
Summary In previous studies we have found that several anions can be transported by an exchange process in rabbit ileal brush border membranes. We demonstrated exchanges of Cl for OH or HCO3, SO4 for OH, oxalate for OH, and oxalate for Cl. The purpose of these studies was to determine the number of distinct carriers mediating these exchanges. We utilized substrate and inhibitor specificity studies to distinguish between different anion exchange transporters. We conclude that SO4OH and oxalate: OH exchange occur on the same carrier because: (i) pH-gradient stimulated transport of both14C-oxalate and35SO4 were equally sensitive tocis-inhibition by unlabeled SO4 or oxalate; and (ii) both were inhibited equally by K. We conclude that oxalate: OH and oxalate: Cl exchanges occur on different carriers because: (i) Cl or SO4 caused unequalcis-inhibition of these two exchanges; and (ii) as compared to oxalate: Cl exchange, oxalate: OH exchange was more sensitive to inhibition by probenecid and K and less sensitive to inhibition by bumetanide. Finally, we conclude that oxalate: Cl exchange and ClHCO3 exchange occur on different carriers because: (i) ClHCO3 exchange was almost completely insensitive tocis-inhibition by oxalate; and (ii) oxalate: Cl exchange was more sensitive to inhibition by DIDS and bumetanide than ClHCO3 exchange. Thus we have found that there are at least three separate anion exchangers on rabbit ileal brush border: (i) a ClHCO3 exchanger; (ii) a SO4OH exchanger, which also transports oxalate; and (iii) an oxalate: Cl exchanger. 相似文献
2.
Bjarne G. Munck 《The Journal of membrane biology》1985,83(1-2):15-24
Summary The transport of -alanine and MeAIB and their effects as inhibitors of the transport of alanine, leucine and lysine across the brush-border membrane of the intact epithelium from the rabbit's distal ileum has been examined. Two separate transport systems have been characterized: 1) A sodium-dependent, -alanine-accepting system, which is a high-affinity transport system for -amino-monocarboxylic acids (neutral a.a.) and for cationic a.a., accepts non--amino acids as well as non--imino acids, is moderately stereospecific, and for which the affinity of a neutral a.a. is greatly reduced by N-methylation. 2) A sodium-dependent transport system for imino acids, which is inaccessible to cationic amino acids and non--amino acids but accepts cyclic, non--imino acids, is moderately stereospecific, and for which neutral a.a. have much lower affinities than their N-methylated derivatives. On the basis of the observations of this and the preceding paper five transport systems for amino acids are ascribed to the rabbit ileum. Some discrepancies between the present results and those obtained with brush-border membrane microvesicles from the rabbit small intestine are discussed. 相似文献
3.
Jane E. Langridge-Smith Joseph H. Sellin Michael Field 《The Journal of membrane biology》1983,72(1-2):131-139
Summary In intact ileal mucosa, uptake of SO4 across the brush border membrane requires the presence of Na and is saturable, withK1/2=1.3mm at 140mm Na (P.L. Smith, S.A. Orellana & M. Field, 1981.J. Membrane Biol.
63:199–206). The present study examines the substrate specificities and transport stoichiometry of the Na-dependent SO4 uptake process. The effects of variations in medium anion and cation composition on lumen-to-epithelium influx of SO4 (J
me
SO4
) were determined under short-circuit conditions.J
me
SO4
is inhibited by thiosulfate, but not by phosphate, methylsulfate, vanadate or taurocholate. Cl is weakly inhibitory. Uptake of SO4 is poorly supported by Li, and is unaffected by K, indicating a specific dependence on Na. At low SO4 concentration (0.22mm),J
me
SO4
is a hyperbolic function of medium Na concentration; the corresponding Hill plot is linear with a slope of 1.0, suggesting a transport stoichiometry of 1 Na: 1 SO4. At high SO4 concentration (6.7mm), the Na-dependent SO4 velocity curve is sigmoidal and yields a Hill plot which is again linear but has a slope of 1.56, suggesting transport of more than 1 Na per SO4. SO4 uptake in presence of Na exhibits a dependence on medium pH. At 0.22mm SO4 and 140mm Na,J
me
SO4
was doubled by lowering pH from 7.4 to 6.8. However, at 6.7mm SO4 and 140mm Na, changing pH had no effect onJ
me
SO4
over the range 6.8 to 8.5. The pH dependence ofJ
me
SO4
at 6.7mm SO4 was restored when medium Na was lowered to 3mm, suggesting that pH sensitivity is a function of the concentration of preformed NaSO
4
–
ion pair. The results suggest that SO4 influx across the ileal brush border occurs by electroneutral Na+/NaSO
4
–
or Na+/H+/SO
4
2–
cotransport, the former being favored by high concentrations of Na and SO4. 相似文献
4.
In view of the likely production of monohydroxyeicosatetraenoic acid (HETE's) in bronchial asthma, the role of these lipoxygenase products in the development of a classical clinical element of airway disease, namely airway hyperreactivity, has been investigated. Tracheas removed from guinea-pigs actively sensitized to ovalbumin produced, upon antigenic challenge (0.01 μg/ml), a 17-fold increase (0.97 ± 0.34 ng/ml to 16.73 ± 1.58 ng/ml) in the amount of 5-hydroxyeicosatetraenoic acid (5-HETE) as measured by radioimmunoassay of the tissue-bath fluid, indicating that this tissue is capable of producing 5-HETE. While 5-HETE alone, at concentrations equal to or greater than those found during the above antigenic response (0.001 to 1.0 μM), failed to produce intrinsic contractions of normal, nonsensitized guinea-pig trachea, a 30 min pretreatment with 5-HETE (1.0 μM) enhanced subsequent LTD4-induced contractions. Pretreatment with either 12- or 15-HETE, at similar concentrations and conditions, failed to potentiate LTD4 concentration-response curves. The effect of 5-HETE was time-dependent, since pretreatment for either 15 or 60 min had little or no effect on subsequent LTD4 responses. Also, the 5-HETE-induced enhancement seemed specific fot LTD4, since contractions to LTC4 (in the presence of l-serine borate), acetylcholine, histamine, PGD2 or U-46619 were unaffected by 5-HETE. Therefore, 5-HETE may have a role in the development of airway hyperreactivity by interacting with released LTD4 to exacerbate airway smooth muscle contraction in asthma. 相似文献
5.
烟碱对乙酰胆碱诱发豚鼠回肠收缩作用的调节 总被引:3,自引:0,他引:3
在离休豚鼠回肠标本上,ACh诱发双相收缩反应:早期相收缩反应持续时间短,与神经节N受体有关;后期相收缩反应持续时间长,与平滑肌M受体有关。烟碱10μmol/L预孵育后,标本对烟碱激动神经节N受体诱发的收缩作用产生急性耐受,而ACh激动平滑肌M受体诱发的收缩作用增强。 相似文献
6.
Sandrine Sagan Hubert Josien Philippe Karoyan Alié Brunissen Gérard Chassaing Solange Lavielle 《Bioorganic & medicinal chemistry》1996,4(12):2167-2178
The action of rotameric probes introduced either in position 7 or 8 in the sequence of substance P (SP) was investigated, i.e.
-tetrahydroisoquinoleic acid (Tic),
-fluorenylglycine (Flg),
-diphenylalanine (Dip), the diastereoisomers of
-1-indanylglycine (Ing) and
-benz[ƒ]indanylglycine (Bfi), the Z- and E-isomers of dehydrophenylalanine and dehydronaphthylalanine (ΔZPhe, ΔEPhe, ΔZNal, ΔENal) and
(Dmp). The aim of this study was the topographical characterization of the binding subsites of human NK-1 receptor expressed in CHO cells, especially the S7 and S8 subsites, corresponding to residues Phe7 and Phe8 of substance P. According to the binding potencies of these substituted-SP analogues, the S7 binding subsite is smaller than the S8 subsite: the S7 subsite accepts only one aromatic nucleus, while the S8 can accommodate three coplanar nuclei altogether. These findings are compatible with the idea that the S8 binding subsite may reside in the extracellular loops of the hNK-1 receptor. NK-1 agonists bind to human NK-1 receptor and activate the production of both inositol phosphates and cyclic AMP. As already quoted for septide, [pGlu6, Pro9]SP(6–11), discrepancies are observed between affinity (Ki) and activity (EC50) values for IPs production. While a weak correlation between Ki and EC50 values for IPs production could be found (r = 0.70), an excellent correlation could be demonstrated between their affinities (Ki) and their potencies (EC50) for cAMP production (r = 0.97). The high potency (EC50) observed for ‘septide-like’ molecules on PI hydrolysis, compared to their affinity is not an artefact related to the high level of NK-1 receptors expressed on CHO cells since a good correlation was found between EC50 values obtained for PI hydrolysis and those measured for spasmogenic activity in guinea pig ileum bioassay (r = 0.94).
According to the binding potencies of constrained analogues of phenylalanine, the S7 binding subsite of human NK-1 receptor is small, whereas the S8, which can accommodate three coplanar nuclei, might probably reside in the extracellular loop. The discrepancies observed between affinity (Ki) and activity (EC50) values for IPs production are not an artefact of CHO cells since a good correlation was found between EC50 for PI hydrolysis and those measured in guinea pig ileum bioassay. 相似文献
7.
Chronic administration of l-prolyl-l-leucyl-glycinamide (MIF-I) to mice slightly reduced morphine's antinociceptive activity in the hot-plate test and modified the biphasic motor activity response to morphine. MIF-I antagonized the initial depression of activity and potentiated the increased motor activity phase. Chronic treatment of rats with MIF-I prevented morphine's antinociceptive activity in the tail flick test. MIF-I partly antagonized the inhibition by morphine of the coaxially stimulated guinea-pig ileum preparation. The inhibition of the ileum produced by ethylketocyclazocine was weakly antagonized by MIF-I. In contrast, MIF-I had no effect on the inhibition of the stimulated mouse vas deferens produced by Leu-enkephalin. The findings show that MIF-I weakly and selectively inhibits μ-type opiate receptors which suggests that MIF-I could be an endogenous inhibitor of opiate receptors. 相似文献
8.
Philip L. Smith Stephanie A. Orellana Michael Field M.D. 《The Journal of membrane biology》1981,63(3):199-206
Summary Unidirectional fluxes of35SO4 across and into rabbit ileal epithelium were measured under short-circuit conditions, mostly at a medium SO4 concentration of 2.4mm. Unidirectional mucosa (m)-to-serosa (s) ands-to-m fluxes (J
ms,J
sm) were 0.456 and 0.067 moles hr–1 cm–2, respectively.J
ms was 2.7 times higher in distal ileum than in mid-jejunum. Ouabain abolished net SO4 transport (J
net) by reducingJ
ms. Epinephrine, a stimulus of Cl absorption, had no effect on SO4 fluxes. Theophylline, a stimulus of Cl secretion, reducedJ
ms without affectingJ
sm, causing a 33% reduction inJ
net. Other secretory stimuli (8-Br-cAMP, heat-stable enterotoxin, Ca-ionophore A23187) had similar effects. Replacement of all Cl with gluconate markedly reducedJ
net through both a decrease inJ
ms and an increase inJ
sm. The anion-exchange inhibitor, 4-acetoamido-4-isothiocyano-2,2-sulfonic acid stilbene (SITS), when added to the serosal side, reducedJ
ms by 94%, nearly abolishingJ
net. SITS also decreasedJ
sm by 75%. Mucosal SITS (50 m) was ineffective. 4,4-diisothiocyano-2,2-sulfonic acid stilbene (DIDS) had effects similar to SITS but was less potent. Measurements of initial rates of epithelial uptake from the luminal side (J
me) revealed the following: (1)J
me is a saturable function of medium concentration with aV
max of 0.94 moles hr–1 cm–2 and aK
1/2 of 1.3mm; (2) replacing all Na with choline abolishedJ
me; (3) replacing all Cl with gluconate increasedJ
me by 40%; (4) serosal SITS had no effect onJ
me; and (5) stimuli of Cl secretion had no effect onJ
me or increased it slightly. Determination of cell SO4 with35SO4 indicated that, at steady-state, the average mucosal concentration is 1.1 mmoles per liter cell water, less than half the medium concentration. Cell SO4 was increased to 3.0mm by adding SITS to the serosal side. Despite net transport rates greater than 1.4 Eq hr–1 cm–2, neither addition of SO4 to the SO4-free medium nor addition of SITS to SO4-containing medium altered short-circuit current. The results suggest that (1) ileal SO4 absorption consists of Na-coupled influx (symport) across the brush border and Cl-coupled efflux (antiport) across the basolateral membrane; (2) the overall process is electrically neutral; (3) the medium-to-cell Cl concentration difference may provide part of the driving force for net SO4 absorption; and (4) since agents affecting Cl fluxes (both absorptive and secretory) have little effect on SO4 fluxes, the mechanisms for their transcellular transports are under separate regulation. 相似文献
9.
Experiments were made on isolated tissues from guinea-pig to test the hypothesis that the distomers of rac-β2-adrenoceptor agonists induce airway hyperreactivity. Tracheal strip preparations were contracted with carbachol. Both rac- and (R;R)-formoterol (2 and 1 μmol/1, respectively) produced an immediate relaxation, followed by a slow recovery of tone. (S;S)-Formoterol (2 μmol/1) had no effect on smooth muscle tone. Similar results were obtained with the enantiomers of terbutaline. In other strip preparations of the trachea or the main bronchi, cholinergic or nonadrenergic/noncholinergic (NANC) excitatory responses were evoked by electrical field-stimulation. The eutomers, (R;R)-formoterol and (R)-terbutaline, inhibited concentration-dependently both cholinergic and NANC-induced contractions. The distomers, (S;S)-formoterol and (S)-terbutaline, showed qualitatively the same effects but were about 1,000 times less potent than the corresponding eutomer. In a third series of experiments, either enantiomer of formoterol was administered to an electrically stimulated vagus nerve-trachea tube preparation. The nerve-induced contractions were inhibited by both enantiomers, but (S;S)-formoterol was about 1,000 times less potent than (R;R)-formoterol. For both enantiomers of formoterol, about tenfold higher concentration was required to obtain the same degree of inhibition when given intratracheally as compared with administration in the external medium. There was no indication in any of the experimental approaches that (S;S)-formoterol or (S)-terbutaline might enhance the response to cholinergic or NANC-related stimuli. Chirality 8:567–573, 1996. © 1997 Wiley-Liss, Inc. 相似文献
10.
Masakazu Takahashi Shigeo Moriguchi Toshiko Minami Hiroyuki Suganuma Akira Shiota Yasuyuki Takenaka Fumito Tani Ryuzo Sasaki Masaaki Yoshikawa 《Letters in Peptide Science》1998,5(1):29-35
Albutensin A is an ileum-contracting peptide derived from serum albumin. The sequences of bovine, human and porcine albutensin A are ALKAWSVAR, AFKAWAVAR, and AFKAWSLAR, respectively. These albutensin A homologs all exhibited biphasic ileal contractions in the longitudinal strips of guinea pig ileum. The order of potency in the contraction was porcine > bovine > human homologs. The ileal contraction profiles were similar to those of oryzatensin and casoxin C, agonist peptides for complement C3a receptors derived from rice albumin and bovine -casein, respectively. All three homologs of albutensin A have homology with the COOH-terminal sequences of complements C3a and C5a, which are essential for their activities; porcine albutensin A showed the highest homology. Indeed, porcine albutensin A was confirmed to act through both C3a and C5a receptors by a radioreceptor assay and cross-desensitization in the ileal contraction. In addition, bovine and human homologs also showed affinity for both receptors. This study suggests that a bioactive peptide acting through both C3a and C5a receptors is released by the proteolytic cleavage of serum proteins other than complement components. 相似文献