全文获取类型
收费全文 | 201篇 |
免费 | 13篇 |
国内免费 | 1篇 |
专业分类
基础医学 | 10篇 |
临床医学 | 7篇 |
内科学 | 11篇 |
神经病学 | 2篇 |
特种医学 | 6篇 |
外科学 | 2篇 |
综合类 | 36篇 |
预防医学 | 6篇 |
药学 | 89篇 |
中国医学 | 46篇 |
出版年
2024年 | 1篇 |
2023年 | 3篇 |
2022年 | 3篇 |
2021年 | 1篇 |
2020年 | 3篇 |
2018年 | 2篇 |
2017年 | 3篇 |
2016年 | 2篇 |
2015年 | 3篇 |
2014年 | 7篇 |
2013年 | 13篇 |
2012年 | 22篇 |
2011年 | 11篇 |
2010年 | 9篇 |
2009年 | 8篇 |
2008年 | 13篇 |
2007年 | 12篇 |
2006年 | 8篇 |
2005年 | 8篇 |
2004年 | 7篇 |
2003年 | 7篇 |
2002年 | 4篇 |
2001年 | 4篇 |
2000年 | 1篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 8篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1974年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有215条查询结果,搜索用时 31 毫秒
31.
本文报道在一定pH值条件下,乌头碱水解为二个一级反应的连串反应。反应被氢氧根离子催化。两步水解反应速度常数均随介质pH值的降低而增大,速度常数与pH呈抛物线关系。在碱性溶液中,两步反应速度常数均随离子強度增大而逐渐减小,反应呈较强的动力学盐效应。在中性和酸性溶液中,盐效应很弱。在pH为5.21,6.95和8.01时,第一步和第二步反应的活化能分别为104.0±2.2,94.1±0.8,73.9±0.6 KJ·mol-1和104.9±1.3,83.8±0.6,57.3±0.4 KJ·mol-1。 相似文献
32.
33.
《Xenobiotica; the fate of foreign compounds in biological systems》2013,43(12):955-963
1. The objective of this study was to investigate the effects of diammonium glycyrrhizinate on the pharmacokinetics of aconitine in rats and the potential mechanism.2. After oral administration of diammonium glycyrrhizinate (50?mg kg?1), the peak plasma concentration (Cmax), area under the plasma concentration–time curve from zero to time τ (AUC0–τ), and absolute bioavailability of aconitine (0.2?mg kg?1) significantly increased 1.64-, 1.63- and 1.85-fold, respectively, but there was no significant change in half life (t1/2) or clearance (CL). In the other two routes of administration via the tail vein and hepatic portal vein, diammonium glycyrrhizinate (15?mg kg?1) did not affect any of the pharmacokinetic parameters of aconitine (0.02?mg kg?1). Thus, diammonium glycyrrhizinate can enhance the absorption of aconitine, leading to higher oral bioavailability and plasma levels, but it does not influence its elimination.3. Moreover, an in vitro everted gut sac model and Ussing chamber model were used to investigate the potential mechanism. Results from bidirectional transport and inhibition studies demonstrated that P-glycoprotein was the main efflux transporter involved in the absorption of aconitine in rats. The absorption enhancement effect of diammonium glycyrrhizinate should be mainly attributed to inhibiting the activity of P-glycoprotein rather than to the influence on the paracellular or transcellular transport. 相似文献
34.
Aconitine (AC) is a highly toxic compound present in plants of the genus Aconitum. The transcellular transport mechanism of AC was investigated using Caco-2 cells. The flux of AC was time- and concentration-dependent in both apical-to-basolateral and the reverse direction. The efflux of AC was more than two-fold that in the opposite direction. The influx of AC was temperature-, pH- and Na+-dependent. Glucose markedly decreased the absorption of AC. However, the efflux of AC was temperature- and pH-dependent, but Na+-independent. Cyclosporin A and verapamil, both inhibitors of P-glycoprotein (P-gp), significantly decreased the efflux of AC. In addition, MK-571, an inhibitor of multidrug resistance-associated protein 2 (MRP2), exhibited the same trend but to a lesser extent. These results indicate that both the influx and efflux of AC across Caco-2 monolayers were through an active process. A pH-dependent carrier-mediated transport system was the major absorption mechanism and a sodium-dependent glucose transporter may be involved. The active efflux of AC across Caco-2 cells was mediated mainly by ABC-transporter P-gp. It is involved in reducing the toxicity of AC to organisms and is the major reasons for the poor absorption of AC in vivo. 相似文献
35.
36.
Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells 总被引:2,自引:0,他引:2
The effects of aconitine (ACO), a highly toxic alkaloid, on ion currents in differentiated NG108-15 neuronal cells were investigated in this study. ACO (0.3-30 microM) suppressed the amplitude of delayed rectifier K+ current (I K(DR)) in a concentration-dependent manner with an IC50 value of 3.1 microM. The presence of ACO enhanced the rate and extent of I K(DR) inactivation, although it had no effect on the initial activation phase of I K(DR). It could shift the inactivation curve of I K(DR) to a hyperpolarized potential with no change in the slope factor. Cumulative inactivation for I K(DR) was also enhanced by ACO. Orphenadrine (30 microM) or methyllycaconitine (30 microM) slightly suppressed I K(DR) without modifying current decay. ACO (10 microM) had an inhibitory effect on voltage-dependent Na+ current (I Na). Under current-clamp recordings, ACO increased the firing and widening of action potentials in these cells. With the aid of the minimal binding scheme, the ACO actions on I K(DR) was quantitatively provided with a dissociation constant of 0.6 microM. A modeled cell was designed to duplicate its inhibitory effect on spontaneous pacemaking. ACO also blocked I K(DR) in neuroblastoma SH-SY5Y cells. Taken together, the experimental data and simulations show that ACO can block delayed rectifier K+ channels of neurons in a concentration- and state-dependent manner. Changes in action potentials induced by ACO in neurons in vivo can be explained mainly by its blocking actions on I K(DR) and I Na. 相似文献
37.
The present study established a model of RyR2 knockdown cardiomyocytes and elucidated the role of RyR2 in aconitine-induced arrhythmia. Cardiomyocytes were obtained from hearts of neonatal Sprague–Dawlay rats. siRNAs were used to down-regulate RyR2 expression. Reduction of RyR2 expression was documented by RT-PCR, western blot, and immunofluorescence. Ca2+ signals were investigated by measuring the relative intracellular Ca2+ concentration, spontaneous Ca2+ oscillations, caffeine-induced Ca2+ release, and L-type Ca2+ currents. In normal cardiomyocytes, steady and periodic spontaneous Ca2+ oscillations were observed, and the baseline [Ca2+]i remained at the low level. Exposure to 3 μM aconitine increased the frequency and decreased the amplitude of Ca2+ oscillations; the baseline [Ca2+]i and the level of caffeine-induced Ca2+ release were increased but the L-type Ca2+ currents were inhibited after application of 3 μM aconitine for 5 min. In RyR2 knockdown cardiomyocytes, the steady and periodic spontaneous Ca2+ oscillations almost disappeared, but were re-induced by aconitine without affecting the baseline [Ca2+]i level; the level of caffeine-induced Ca2+ release was increased but L-type Ca2+ currents were inhibited. Alterations of RyR2 are important consequences of aconitine-stimulation and activation of RyR2 appear to have a direct relationship with aconitine-induced arrhythmias. The present study demonstrates a potential method for preventing aconitine-induced arrhythmias by inhibiting Ca2+ leakage through the sarcoplasmic reticulum RyR2 channel. 相似文献
38.
Ethnopharmacological relevance
Aconitum has been widely used to treat various diseases in China for a long time. However, improper use of this drug results in severe intoxication. Aconitine (ACO), a diterpenoid alkaloid from aconitum, mainly contributes to cardio-toxic effects of aconitum and has also been commonly known to induce arrhythmias in animal models. However, its pro-arrhythmic mechanisms are not clear.Aim of the study
The effects of ACO on HERG and Kv1.5 channels were investigated.Materials and methods
HERG and Kv1.5 channels were expressed in Xenopus laevis oocytes, and the resulting currents were recorded using a two-microelectrode voltage clamp technique.Results
In HERG channels, ACO exhibited a blockade in a voltage- and time-dependent manner. The blockade was enhanced by further activation of currents, which were consistent with an open-channel blockade. In Kv1.5 channels, ACO produced a voltage-, time-, and frequency-dependent inhibition. The blockade was enhanced by higher rates of stimulation, consistent with preferential binding of the drug to the open state. In addition, ACO blocked Kv1.5 and HERG channels in a concentration-dependent manner with an IC50 of 0.796 ± 0.123 and 1.801 ± 0.332 μM, respectively.Conclusions
ACO blocks HERG and Kv1.5 potassium channels in the open state. Blockade of potassium channels, particular the HERG channel, may be one of the important mechanisms of how ACO induces arrhythmias. 相似文献39.
目的:探讨附子中3种双酯型生物碱提取的影响因素,确定适宜的提取条件。方法:采用HPLC法测定中乌头碱、乌头碱和次乌头碱的含量,采用单因素试验法,对附子双酯型生物碱的提取工艺进行研究。结果:最佳双酯型生物碱提取工艺为:在15℃条件下,将附子粗粉置于10倍无水乙醇中冷浸3次,每次1 d,双酯型生物碱收率为0.57%,质量分数为18.81%,其中中乌头碱、乌头碱和次乌头碱收率分别为0.16%、0.032%和0.38%。结论:该提取方法高效、低毒、经济、操作方便,适合工业化生产。 相似文献
40.
目的对附桂通便颗粒中苯甲酰新乌头原碱、新乌头碱进行含量测定。方法运用高效液相色谱法(HPLC),Kromasil C18柱(250 mm×4.6 mm,5μm),流动相为0.015%二乙胺-乙腈溶液,线性梯度洗脱,流速为1.0 mL/min,柱温35℃,检测波长240 nm。结果苯甲酰新乌头原碱、新乌头碱分别在0.088 8-0.888 0μg(r=0.999 8)、0.199 0-1.990 0μg(r=0.999 8)范围内,具有良好的线性关系;平均加样回收率依次为99.11%、99.13%,相对标准偏差(RSD)分别为0.76%、1.61%。结论该方法快速、简便,重现性好,可作为该制剂的定量分析方法。 相似文献