全文获取类型
收费全文 | 223篇 |
免费 | 2篇 |
国内免费 | 5篇 |
专业分类
耳鼻咽喉 | 1篇 |
妇产科学 | 2篇 |
基础医学 | 25篇 |
口腔科学 | 2篇 |
临床医学 | 5篇 |
内科学 | 24篇 |
皮肤病学 | 4篇 |
神经病学 | 22篇 |
外科学 | 32篇 |
综合类 | 17篇 |
预防医学 | 7篇 |
眼科学 | 5篇 |
药学 | 82篇 |
中国医学 | 2篇 |
出版年
2023年 | 1篇 |
2022年 | 7篇 |
2021年 | 2篇 |
2020年 | 4篇 |
2019年 | 4篇 |
2018年 | 6篇 |
2017年 | 3篇 |
2016年 | 8篇 |
2015年 | 6篇 |
2014年 | 8篇 |
2013年 | 12篇 |
2012年 | 12篇 |
2011年 | 9篇 |
2010年 | 5篇 |
2009年 | 6篇 |
2008年 | 5篇 |
2007年 | 9篇 |
2006年 | 5篇 |
2005年 | 9篇 |
2004年 | 6篇 |
2003年 | 3篇 |
2002年 | 1篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 6篇 |
1998年 | 5篇 |
1997年 | 8篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 1篇 |
1992年 | 6篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1989年 | 7篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 1篇 |
1984年 | 6篇 |
1983年 | 1篇 |
1982年 | 6篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1978年 | 8篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1972年 | 2篇 |
排序方式: 共有230条查询结果,搜索用时 187 毫秒
211.
C. M. Bradshaw M. J. Stoker E. Szabadi 《Naunyn-Schmiedeberg's archives of pharmacology》1982,320(3):230-234
Summary The technique of microelectrophoresis was used in order to examine the effects of clonidine on single neurones in the somatosensory cortex of the rat, and to compare its actions with those of noradrenaline and phenylephrine. Clonidine evoked only excitatory responses on cortical neurones. The clonidine-sensitive neurones were also excited by noradrenaline and phenylephrine. Clonidine had a consistently lower apparent potency than either noradrenaline or phenylcphrine. Responses to clonidine had a slower time-course than responses to the other two adrenoceptor agonists, both the latencies to onset and the recovery times being longer for responses to clonidine than for responses to noradrenaline and phenylephrine. When the mobilities of clonidine and phenylephrine were compared using an in vitro method, no significant difference was found between the mobilities of the two ionic species, suggesting that they have similar transport numbers. Thus the difference between the potencies and time-courses of responses to clonidine and phenylephrine are presumably of biological origin. Responses to clonidine were antagonised by microelectrophoretically applied prazosin; responses to phenylephrine were equally antagonised, while responses to acetylcholine were not affected. Clonidine could reversibly antagonise excitatory responses to both noradrenaline and phenylephrine, whithout affecting responses to acetylcholine. The results suggest that clonidine may act as a partial agonist at excitatory 1-adrenoceptors on cortical neurones. 相似文献
212.
Sheila A. Doggrell 《Naunyn-Schmiedeberg's archives of pharmacology》1992,346(3):294-302
Summary On the endothelium-intact rat aorta some studies have shown prazosin to cause nonparallel rightward shifts of 1-adrenoceptor agonist response curves. The aim of the present study was to analyze the inhibitory effect of prazosin on the phenylephrine responses of the endothelium-intact and endothelium-denuded rat aorta. Firstly I used phenoxybenzamine treatment to characterize the phenylephrine responses. The KA values for phenylephrine were 0.13–0.18 M and 0.07–0.16 M in the endothelium-intact and endothelium-denuded rat aorta, respectively. In order to produce maximal responses of the endothelium-intact or — denuded preparation, phenylephrine had to occupy 95–99% of the 1-adrenoceptors.Secondly I compared the inhibitory effects of phentolamine and prazosin on the endothelium-intact rat aorta. Phentolamine at 0.1 and 1 M caused parallel rightward shifts of phenylephrine response curves with no effect on phenylephrine maximal responses (phentolamine pA2 = 7.9). The inhibitory effects of phentolamine were readily reversible. Prazosin at 0.1–10 nM caused nonparallel rightward shifts of the phenylephrine response curves with a depression of the maximal response. These inhibitory effects of prazosin were either irreversible or only very slowly reversible in drug-free solution and slowly reversible in the presence of phentolamine. Ninety min was required for the inhibitory effect of prazosin to reach equilibrium whereas phentolamine was at equilibrium after 45 min. Finally I have characterized the inhibitory actions of prazosin on the endothelium-denuded rat aorta. Prazosin caused parallel rightward shifts of phenylephrine response curves with no effect on phenylephrine maximal responses. The inhibitory effects of prazosin were at equilibrium after 45 min and were readily reversible.In conclusion prazosin is a readily reversible 1-adrenoceptor antagonist in the endothelium-denuded but not in the endothelium-intact rat aorta. It seems likely that the endothelium accumulates or binds prazosin strongly so that the inhibitory action of prazosin is apparently slowly reversible in the endothelium-intact rat aorta. 相似文献
213.
H. R. Schwietert M. A. M. Gouw D. Wilhelm B. Wilffert P. A. van Zwieten 《Naunyn-Schmiedeberg's archives of pharmacology》1991,343(5):463-471
Summary The purpose of this investigation was to determine whether 1-adrenoceptor subtypes (co)exist in the rat portal vein and, if so, whether they could be functionally associated with the phasic and tonic types of contraction as a response to 1-adrenoceptor stimulation by phenylephrine.A low Ca2+ concentration (0.9 mmol/l) in the Tyrode solution enabled us to quantify changes both in the phasic myogenic activity and in the basal tone of the rat portal vein preparation very precisely. We used both competitive and non-competitive -adrenoceptor antagonists which have been employed successfully by other investigators to discriminate between 1-adrenoceptor subtypes in vascular and other tissues. Schild analysis showed that the competitive -adrenoceptor antagonists prazosin, phentolamine, yohimbine, corynanthine, idazoxan, rauwolscine and 5-methyl-urapidil could not distinguish between the phasic and tonic responses to phenylephrine and/or different 1-adrenoceptor subtypes in the rat portal vein. However, when we compared our pA2 values with those found to be representative indicators according to subclassifications based on the use of selective antagonists in different tissues, the 1-adrenoceptors in the rat portal vein appeared to belong to the 1L- or 1a-subtype. This subclassification was not in accordance with the data obtained with the irreversible -cadrenoceptor antagonist chloroethylclonidine. However, the validity of this alkylating agent as a tool for receptor classification was restricted, at least in the rat portal vein, by its effects on receptor reserve. In contrast to the competitive -adrenoceptor antagonists, the irreversible -adrenoceptor antagonists phenoxybenzamine and chloroethylclonidine could indeed discriminate between the phasic and tonic types of contraction in response to 1-adrenoceptor stimulation by phenylephrine, indicating two different receptor reserves for phenylephrine for the two types of responses.In conclusion, both the phasic and tonic types of contraction elicited by phenylephrine in the longitudinal smooth muscle of the rat portal vein appear to be mediated by one particular 1-adrenoceptor subtype as defined by Schild analysis with selective, competitive -adrenoceptor antagonists. However, using the method of receptor alkylation with phenoxybenzamine, two different affinity constants for the two types of responses could be calculated for phenylephrine. This may reflect the involvement of two different subtypes of 1-adrenoceptors or more probably, the existence of only one 1-adrenoceptor subtype, which is coupled with two different intrinsic efficacies to the effector pathways mediating the phasic and tonic responses, respectively.
Send offprint requests to H. R. Schwietert at the above address 相似文献
214.
Rudolf Ertl Ulrich Jahnel Hermann Nawrath Edward Carmeliet Johan Vereecke 《Naunyn-Schmiedeberg's archives of pharmacology》1991,344(5):574-581
Summary Stimulation of 1-adrenoceptors evokes a different pattern of inotropic responses in atrial and ventricular heart muscle preparations from rats. The inotropic effects are accompanied by different changes in membrane potential. In an attempt to clarify the question whether or to which extent these events are causally related, the effects of phenylephrine on force of contraction, transmembrane potential, Ca2+ current (ICa) and K+ currents were comparatively studied in either tissue.In atrial preparations, phenylephrine 10 mol/l caused an increase in force of contraction, a marked prolongation of the action potential duration and a depolarization of the membrane at rest. In the ventricle, however, the addition of phenylephrine 10 mol/l produced first a decline in force of contraction associated with a hyperpolarization of the membrane and a reduction in the action potential duration. These changes were followed by an increase in force,of contraction and a slight prolongation of the action potential, whereas the resting membrane potential remained increased. The hyperpolarization was eliminated in the presence of ouabain 100 mol/l.In enzymatically isolated atrial and ventricular myocytes, the whole-cell voltage clamp technique was used to study membrane currents on exposure to phenylephrine. Phenylephrine 30 mol/l did not affect the magnitude of ICa in either cell type. Transient and steady state K+ outward currents, however, were significantly diminished to a similar extent in atrial and in ventricular myocytes.It is concluded that the positive inotropic effect of 1-adrenoceptor stimulation in the rat atrium is related to an increase in action potential duration and a decrease in resting membrane potential due to a decrease in K+ currents. In the ventricle, phenylephrine additionally activates the Na+/K+ pump thereby hyperpolarizing the membrane. The rapid onset of pump stimulation seems to overwhelm, in the beginning, the phenylephrine-induced decrease in K+ conductance and therefore to evoke a transient negative inotropic effect.It is assumed that phenylephrine can alter the intracellular Ca2+ concentration due to changes in the action potential duration. The way how Ca 2+ enters the cell remains speculative, since direct changes of Ica were not detected. The more complicated changes in membrane potential in the ventricle suggest that also other mechanisms for the positive inotropic response to phenylephrine must be considered.
Send offprint requests to H. Nawrath at the above address 相似文献
215.
Kashimura O 《Environmental health and preventive medicine》1998,3(2):78-82
We investigated the responses of thoracic aortae to adrenergic contraction and endothelium-dependent relaxation following
chronic exposure to cold in rats. Two groups (CA, cold-acclimated for 12 weeks at 5 °C; WA, warm-acclimated for 12 weeks at
24 °C) of 10 male Sprague-Dawley rats were used. After anesthesia, the thoracic aortae (4 mm long) were isolated and the vascular
tension was measured with a force transducer. The dose-response relations for aortic responses to norepinephrine (NE), phenylephrine
(PE) and acetylcholine (Ach) were determined and compared between the CA and the WA groups. In the CA rats, the thoracic aortae
became more sensitive to Ach-induced vasorelaxation. The vascular sensitivities to NE- or PE-induced contraction in the thoracic
aortae were lowered. Chronic exposure to cold decreased NE- and PE-induced vasoconstrictive responses and increased Achinduced
vasorelaxative response of the isolated thoracic aortae, which were suggested to be due to enhanced release of NE-induced
endothelium-derived relaxing factor by up-regulating endothelial α1-adrenoceptors. 相似文献
216.
Hagen Trommer Klaus RaithReinhard H.H. Neubert 《Journal of pharmaceutical and biomedical analysis》2010
The frequently used sympathomimetic drug phenylephrine has been studied by electrospray ionisation-mass spectrometry. The stability of the adrenoceptor agonist was examined by investigations of the pharmaceutically used salts phenylephrine hydrochloride and phenylephrine bitartrate. Photostability has been studied by use of an irradiation equipment emitting a solar radiation spectrum. The experiments were carried out by analysis of aqueous drug solutions before and after irradiation treatment. The phenylephrine derivative with unsaturated side chain originating from the drug by loss of one water molecule has been detected as the major degradation product of both phenylephrine salts the hydrochloride and the bitartrate. Further degradation and oxidation products were detectable already in the full scan mode demonstrating a low stability of the drug. Tandem mass spectrometry and multiple stage mass spectrometry experiments enabled the establishment of fragmentation schemes of both salts for the first time. Irradiation treatment indicated that phenylephrine bitartrate is more prone to degradation than the hydrochloride because of an additional decomposition sensitivity of the tartaric acid counter ion. An interaction between phenylephrine and its counter ion degradation products via a nucleophilic addition mechanism is suggested to be the explanation for the detected ion signals after irradiation treatment of phenylephrine bitartrate. 相似文献
217.
Heat, acid, base, UV radiation and oxidation stress methods were applied to study the stability of cough–cold products containing acetaminophen, phenylephrine or phenylpropanolamine hydrochloride and chlorpheniramine maleate. Liquid chromatography coupled with mass spectrometry was used to analyze the degraded samples and obtain molecular weights information. Different volatile buffers (ammonium bicarbonate and ammonium acetate) were assayed in LC/MS methods and retention times of the analytes were compared with those obtained in HPLC with UV detection employing a conventional sodium phosphate buffer to establish the possibility of results transference between the two systems. 相似文献
218.
219.
220.
Hiroyasu Satoh Keitaro Hashimoto 《Naunyn-Schmiedeberg's archives of pharmacology》1988,337(4):415-422
Effects of methoxamine and phenylephrine on the action potential and the membrane currents in spontaneously beating rabbit sino-atrial node cells were examined by means of a two-microelectrode voltage-clamp technique. Both methoxamine and phenylephrine (10(-4) mol/l) prolonged the cycle length (CL) and the action potential duration (APD), significantly. At concentrations higher than 3 x 10(-4) mol/l, phenylephrine increased the maximum rate of rise of action potential (Vmax) but methoxamine reduced it. Both agents depolarized the maximum diastolic potential (MDP). These changes in the action potential parameters occurred in a concentration-dependent manner. In the presence of phentolamine (10(-5) mol/l), methoxamine (3 x 10(-4) mol/l) did not modify the action potential parameters. Also, phenylephrine did not affect them during exposure to phentolamine (10(-5) mol/l) and pindolol (10(-7) mol/l). In voltage-clamp experiments, at 10(-3) mol/l both methoxamine and phenylephrine slightly increased the slow inward current (Isi), but decreased the time-dependent outward current (Ik). The steady-state activation variable of Ik (p infinity) was unaffected by these agents. The hyperpolarization-activated current (Ih) was suppressed in the presence of methoxamine, but enhanced in the presence of phenylephrine. An additional application of pindolol (10(-7) mol/l) during exposure to phenylephrine (10(-3) mol/l) depressed the action potential amplitude (APA) and Vmax, and prolonged CL slightly. Under the same condition, all the membrane currents (Isi, Ik and Ih) were decreased. In addition, the time courses of decay for Isi were not modified in the absence and the presence of phenylephrine (10(-3) mol/l) and phenylephrine plus pindolol (10(-7) mol/l).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献