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171.
《Clinical and experimental hypertension (New York, N.Y. : 1993)》2013,35(8):1425-1439
Effects of chronic glucocorticoid treatment on arterial baroreflex function and on cardiac β- and vascular α-adrenoceptor-mediated responses were assessed in conscious, unrestrained Wistar-Kyoto rats. Cortisol (25 mg/kg/day) was administered for seven days using a subcutaneous reservoir pump. Arterial baroreflex-cardiac sensitivity was assessed by examining the relationship of the cardiac interbeat interval to the mean arterial blood pressure during phenylephrine or nitroprusside challenge; baroreflex-sympathoneural sensitivity was assessed from the ratio of the increase in the arterial norepinephrine concentration to the decrease in mean arterial pressure at 15 min during intravenous infusion of nitroprusside; cardiac β-adrenoceptor-mediated responsiveness was estimated from heart rate responses to bolus-injected isoproterenol; and vascular α-adrenoceptor-mediated responsiveness was estimated from peak mean arterial pressure responses to bolus-injected phenylephrine. Cortisol treatment increased mean arterial pressure, decreased heart rate, and increased heart rate responses to isoproterenol, whereas baroreflex-vagal sensitivity, baroreflex-sympathoneural sensitivity, and pressor responses to phenylephrine were unaffected. The results indicate that hypertension due to chronic cortisol administration is not associated with decreased sensitivity of the baroreceptor-cardiac reflex. Baroreflex-sympathoneural sensitivity and α1-adrenoceptor responsiveness also remain normal, whereas β-adrenoceptor responsiveness is increased. The findings suggest that the pattern of neurocirculatory adjustment in glucocorticoid hypertension differs from that seen in other forms of hypertension. 相似文献
172.
苯肾上腺素荧光标记物的合成及其生物活性的鉴定 总被引:1,自引:0,他引:1
目的:合成α1-肾上腺素受体特异性激动剂--苯肾上腺素(phenylephrine,PE)荧光标记物,检测其药理学生物活性.方法:用化学合成的方法将绿色荧光染料BODIPY-FL和PE进行微量缩合反应,薄层色谱法分离和纯化,用薄层色谱和质谱分析对其纯度和分子结构进行鉴定.通过分子生物学Western blot方法检测其药理学生物活性.结果:将BODIPY-FL与PE在无水、无氧和避光条件下进行羧合反应,经薄层色谱分离、纯化得到具有荧光的新化合物--BODIPY-FL-PE,结构经紫外光谱和质谱分析得到证实.Western blot实验表明BODIPY-FL-PE与PE同样具有激动α1-肾上腺素受体,使胞外信号调节激酶(extracellular signal-regulated kinase,ERK)激活的药理作用.结论:经微量缩合反应合成的BODIPY-FL-PE具有α1-肾上腺素受体激动剂药理学特性,可以用于肾上腺素受体行为观测,为进一步研究活细胞中肾上腺素受体的动态行为提供了工具. 相似文献
173.
174.
Rationale Peripheral physiologic changes accompany many central pharmacologic manipulations and can interact with brain activity and
cerebral perfusion in complex ways. This considerably complicates the interpretation of drug-induced brain activity changes.
Objectives To evaluate a method whereby drug-induced blood pressure (BP) changes are prevented.
Methods A continuously adjusted infusion of the peripheral vasoconstrictor phenylephrine (PEP) was used to counter-regulate BP changes
elicited by application of the dopamine receptor agonist apomorphine (APO) in the rat. Central effects of APO were measured
using pharmacologic magnetic resonance imaging (phMRI) with blood oxygenation level dependent (BOLD) contrast at a field strength
of 7 T.
Results Compared to a NOPEP control group, the PEP blood pressure clamp successfully prevented BP changes and improved the detectability
of central APO effects. Moreover, APO-induced central changes no longer correlated with BP time courses.
Conclusions The method is suitable for isolating central drug effects from peripherally originating (BP) confounds in high-field functional
magnetic resonance imaging (fMRI) studies. It may also be useful in fMRI studies of autonomic regulation, cognition, and emotion
if the experimental manipulation entails BP changes. 相似文献
175.
In an attempt to determine whether alpha adrenergic agonists sprayed directly over the wound are able to reduce a superficial bleeding, phenylephrine (0.25%), oxymetazoline (0.05 and 0.25%) and saline (0.9%) were tested in a rat model. The study was randomized, controlled and quantitative. A total of four incisions were made in each rat, and each solution was sprayed directly on the incision according to a specific protocol. The bleeding times were measured and summed up. Biases were minimized by the fact that each rat received all four solutions, including the control, in all possible combinations. The mean bleeding time after spraying phenylephrine (0.25%) was significantly shorter than the mean bleeding time after spraying saline (1.90 +/- 0.14 min versus 4.80 +/- 0.43 min, respectively, P < 0.001) and significantly shorter than the mean bleeding time after spraying oxymetazoline (0.05 or 0.25%: 4.46 +/- 0.54 and 5.50 +/- 0.58 min, respectively, P < 0.001). No statistically significant difference was found between the mean bleeding time after spraying oxymetazoline (0.05 or 0.25%) compared with saline. We conclude that sprayed phenylephrine (0.25%) can be used for reducing superficial bleedings. This method is simple, cost-effective, does not cause further trauma to the tissue, and can be used to treat several bleedings simultaneously (especially abrasions and lacerations) with a single application, without the need for direct physical contact with the bleeding sites. The method is apparently safe, but further studies are needed to test the systemic effect of the sprayed solution. 相似文献
176.
Wimalasundera RC Thom SA Regan L Hughes AD 《American journal of obstetrics and gynecology》2005,192(2):625-632
OBJECTIVE: Preeclampsia is a common and serious complication of pregnancy, characterized by maternal hypertension and proteinuria, placental insufficiency, and fetal growth restriction. The purpose of this study was to investigate whether intracellular Ca 2+ ([Ca 2+ ] i ) and contractile responses of vascular smooth muscle to vasoactive agents are altered in preeclampsia compared with normal pregnancy and the nonpregnant state. STUDY DESIGN: Subcutaneous and myometrial resistance arteries from women who had preeclampsia, normal pregnancy, and nonpregnant women were obtained at the time of cesarean section or hysterectomy. Arteries were mounted on an isometric myograph and loaded with the Ca 2+ indicator, fura-2AM, to permit simultaneous measurement of force and [Ca 2+ ] i . Reponses to endothelium-dependent relaxants (acetylcholine and substance P) and vasoconstrictors (depolarizing potassium solution, phenylephrine, and angiotensin II) were examined. RESULTS: The fall in [Ca 2+ ] i and relaxation in response to acetylcholine was significantly inhibited in both myometrial and subcutaneous arteries from preeclamptic women compared with arteries from nonpregnant or normal pregnant women. However, responses to substance P did not differ between the 3 groups. There were no significant differences in [Ca 2+ ] i or force responses to high potassium, phenylephrine, or angiotensin II in myometrial and subcutaneous resistance vessels in women with preeclampsia compared with normal pregnant women. However, force, but not [Ca 2+ ] i responses to angiotensin II, in subcutaneous vessels from normal pregnant and preeclamptic women were reduced compared with subcutaneous arteries from nonpregnant women, indicating that pregnancy is associated with a reduction in Ca 2+ sensitization in this tissue. A similar effect was not seen in myometrial arteries. CONCLUSION: Endothelial function is altered in preeclampsia, with loss of effect of acetylcholine, but not substance P. Vasoconstrictor reactivity is not increased in preeclampsia compared with uncomplicated normal pregnancy, and this is unlikely to be an explanation for the increased peripheral vascular resistance seen in preeclampsia. 相似文献
177.
Topical phenylephrine, an agent used to facilitate nasotracheal intubation and prevent nasal mucosal bleeding, can cause severe hypertension in some patients, secondary to its stimulation of alpha-adrenergic receptors. Moreover, a high incidence of pulmonary edema is found in patients whose phenylephrine administration is followed by treatment with beta-blocking agents. We report a case of acute pulmonary edema in a pediatric patient who developed severe hypertension after the inadvertent administration of a large dose of topical nasal phenylephrine, followed by beta-adrenergic antagonists (esmolol). 相似文献
178.
179.
Three monkeys were trained to slow and to speed heart rate on an operant schedule. After the animals were performing highly reliably they received injections of nitroglycerin or phenylephrine to elicit baroreflexes during control periods and during slowing or speeding sessions. The findings were that each animal reliably attenuated its baroreflex sensitivity and thereby avoided shock. Thus, the data showed that under appropriate behavioral conditions homeostatic adjustments of the cardiovascular system are reduced. 相似文献
180.
Rainer Palluk Wolfgang Hoefke Wolfram Gaida Joachim Mierau Wolf-Dietrich Bechtel 《Naunyn-Schmiedeberg's archives of pharmacology》1986,333(3):277-283
Summary MEN 935 [1-(3-((3-(1-naphthoxy)-2-hydroxypropyl)amino)-3,3-dimethylpropyl)-2-benzimidazolinone-hydrochloride monohydrate, adimolol] is a long acting antihypertensive agent with beta- and alpha-adrenolytic properties. Preliminary experiments in pithed rats had led to the suggestion that the alpha-adrenolytic activity was of the alpha2-subtype. The alpha-adrenolytic properties of MEN 935 were now tested in isolated vascular preparations of rat aorta, rabbit vena ischiadica and rabbit vena cava inferior against the selective alpha1-adrenergic agonist phenylephrine (PE) and the selective alpha2-adrenergic agonist BHT 920 [2-amino-6-allyl-5,6,7,8,-tetrahydro-4H-thiazolo-(4,5-d)azepine]. The experiments were performed in absence and in presence of 5×10–9 mol/l angiotensin II (A II).MEN 935 antagonized contractions to phenylephrine as well as those to B-HT 920 in each vessel. A twofold shift to the right of the concentration-response curves to both agonists was obtained with concentrations between 1.9×10–8 and 1.4×10–5 mol/l, depending on the vessel under investigation. A II modulated the adrenolytic properties of MEN 935 in each vessel. However, irrespective of the presence or absence of A II, no pharmacologically relevant difference between antagonism against PE or B-HT 920 could be seen. In isolated vessels, MEN 935 exerts a nonselective alpha-adrenergic antagonism.In receptor binding studies in rat cerebellar cortex, MEN 935 showed a K
i of 5.2×10–7 mol/l at alpha1-adrenoceptors and a K
i of 1.3×10–5 mol/l at alpha2-adrenoceptors. The K
i values were not influenced by 5×10–9 mol/l A II. These findings demonstrate an alpha1-preference, but again no alpha-subtype selectivity.Parts of the results were presented at the Spring Meeting of the German Pharmacological Society, 1985, in Mainz, FRG, (Palluk R, Hoefke W, Gaida W (1985) Alpha-adrenolytic properties of MEN 935, a long acting beta- and alpha-adrenolytic antihypertensive agent. Naunyn-Schmiedeberg's Arch Pharmacol 329: R 79) 相似文献