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11.
BACKGROUND: It has been previously shown that intrathecal administration of either ouabain or neosdgmine can produce antinociceptive effects. Moreover, ouabain and neostigmine are differently associated with acetylcholine.
OBJECTIVE: It has been hypothesized that intrathecal administration of ouabain, in combination with neostigmine, can produce antinociceptive synergistic effects. Atropine, as a competitive antagonist, was pre-injected to verify the mechanisms of action.
DESIGN, TIME AND SETTING: This study was a randomized, controlled, animal experiment, performed at the State Key Laboratory of Oncology in Southern China between May 2006 and February 2007.
MATERIALS: A total of 102 healthy, adult, Sprague Dawley rats were included. Ouabain and neostigmine (Sigma, USA), as well as atropine (Tanabe Seiyaku, Japan), were also used.
METHODS: Varied doses of ouabain, neostigmine, and a combination of the two were intrathecally injected into rats. Six rats were allotted for each dose group. Intrathecal pretreatment with atropine was tested 10 minutes prior to intrathecal administration of neostigmine or the combination of ouabain and neostigmine.
MAIN OUTCOME MEASURES: Tail-flick tests were performed to measure tail-flick latency (seconds) prior to and after administration. The response in the tail-flick test was expressed as the percentage of maximum possible effect (% MPE), where % MPE = [tail-flick latency after administration (seconds) -mean baseline value for tail-flick latency]/[ 10 seconds - the mean baseline value for tail-flick latency (seconds)] x 100%.
RESULTS: Rat spinal intrathecal administration of either ouabain or neostigmine alone produced antinociceptive effects in a dose-dependent manner. Intrathecally administration of neostigmine (0.05, 0.1, 0.3 μg ) in combination with ouabain (1 μ g ) produced enhanced antinociceptive effects, with a % MPE of 29%, 78%, and 95%, respectively (P 〈 0.05). Intrathecally administration of 0.3μg neost 相似文献
OBJECTIVE: It has been hypothesized that intrathecal administration of ouabain, in combination with neostigmine, can produce antinociceptive synergistic effects. Atropine, as a competitive antagonist, was pre-injected to verify the mechanisms of action.
DESIGN, TIME AND SETTING: This study was a randomized, controlled, animal experiment, performed at the State Key Laboratory of Oncology in Southern China between May 2006 and February 2007.
MATERIALS: A total of 102 healthy, adult, Sprague Dawley rats were included. Ouabain and neostigmine (Sigma, USA), as well as atropine (Tanabe Seiyaku, Japan), were also used.
METHODS: Varied doses of ouabain, neostigmine, and a combination of the two were intrathecally injected into rats. Six rats were allotted for each dose group. Intrathecal pretreatment with atropine was tested 10 minutes prior to intrathecal administration of neostigmine or the combination of ouabain and neostigmine.
MAIN OUTCOME MEASURES: Tail-flick tests were performed to measure tail-flick latency (seconds) prior to and after administration. The response in the tail-flick test was expressed as the percentage of maximum possible effect (% MPE), where % MPE = [tail-flick latency after administration (seconds) -mean baseline value for tail-flick latency]/[ 10 seconds - the mean baseline value for tail-flick latency (seconds)] x 100%.
RESULTS: Rat spinal intrathecal administration of either ouabain or neostigmine alone produced antinociceptive effects in a dose-dependent manner. Intrathecally administration of neostigmine (0.05, 0.1, 0.3 μg ) in combination with ouabain (1 μ g ) produced enhanced antinociceptive effects, with a % MPE of 29%, 78%, and 95%, respectively (P 〈 0.05). Intrathecally administration of 0.3μg neost 相似文献
12.
A. Brogna R. Ferrara G. Scornavacca A. Lombardo A. Bucceri F. Catalano V. Paradisi S. Onorato 《European journal of clinical pharmacology》1989,36(4):411-413
Summary This study examines the role of a neostigmine-induced increase in acetylcholine on the aldosterone stimulating effect of metoclopramide.Six normal male volunteers received the following three treatments in a cross-over randomized sequence: neostigmine, 0.5 mg s.c.; metoclopramide 10 mg i.v.; and neostigmine 0.5 mg s.c., followed by metoclopramide 10 mg i.v.Metoclopramide increased serum aldosterone significantly to 161% of basal level at 15 min. With neostigmine aldosterone levels peaked (129%) significantly at 30 min. In the presence of neostigmine, however, the metoclopramide-induced aldosterone response was blunted significantly.These results would suggest that presynaptic autoreceptors depresses the continued output of acetylcholine, thereby blunting the aldosterone responses to metoclopramide significantly. 相似文献
13.
姜秀英 《菏泽医学专科学校学报》2001,13(1):54-55
目的 观察新斯的明足三里穴封治疗肠麻痹的临床疗效。方法 将 2 89例患者分为对照组 140例 ,给予禁饮食 ,持续胃肠减压 ,补充电解质维持酸碱平衡等一般治疗 ,治疗组 149例在对照组治疗的基础上 ,另给新斯的明足三里穴封。结果 治疗组 132例肠功能恢复时间显著提前。对照组 87例在相近时间内恢复肠功能。两组相比极有显著性差异 (P <0 .0 1)。结论 新斯的明足三里穴封可促进肠胃蠕动 ,见效快 ,无副作用 ,易于操作。 相似文献
14.
目的探讨穴位注射对产后尿潴留的临床治疗效果。方法将157例产后尿潴留产妇随机分为治疗组58例、针灸组49例、肌注组50例,分别接受穴位注射、针灸、肌肉注射治疗,比较3种不同疗法的临床效果。结果治疗组患者治愈率高于其他2组,差异有统计学意义(χ2=7.465,P=0.000);总有效率高于其他2组,差异有统计学意义(χ2=3.124,P=0.002);治疗组患者残尿量为(25.3±6.9)mL,针灸组为(56.4±13.2)mL,肌注组为(47.4±12.8)mL,3组比较差异有统计学意义(F=7.446,P=0.000),治疗组残尿量低于其他2组。结论穴位注射对产后尿潴留具有良好治疗效果,值得临床推广应用。 相似文献
15.
Hitoshi Masuda Michel B. Chancellor Kazunori Kihara Yasuyuki Sakai Fumitaka Koga Hiroshi Azuma William C. De Groat Naoki Yoshimura 《BJU international》2009,104(8):1163-1169
OBJECTIVE
To investigate whether activation of brain and spinal cholinergic pathways affects the micturition reflex in rats.MATERIALS AND METHODS
The effects of intracerebroventricular (i.c.v.) or intrathecal (i.t.) administration of neostigmine as a cholinesterase inhibitor and oxotremorine‐M (OXO‐M) as a muscarinic acetylcholine receptor (mAChRs) agonist, on the micturition reflex were evaluated by infusion cystometrography (CMG) in urethane‐anaesthetized untreated rats or rats pretreated with capsaicin.RESULTS
Neostigmine injected i.c.v. increased bladder capacity (BC) and pressure threshold (PT) dose‐dependently, with an increase in maximum voiding pressure (MVP) and a decrease in voiding efficiency (VE) at higher doses. Also, neostigmine injected i.t. increased the BC and PT dose‐dependently without changing MVP or VE, and these effects were not apparent in capsaicin‐pretreated rats. In both routes, atropine as an antagonist of mAChRs, but not mecamylamine as a nicotinic‐AChR antagonist, almost completely antagonized the effects of neostigmine. The rank order of potencies of the antagonists for increasing effects of BC induced by 1 nmol of neostigmine was: pirenzepine (an M1 mAChR antagonist) = atropine > 4‐DAMP (an M3 mAChR antagonist) >> methoctramine (an M2 mAChR antagonist) and tropicamide (an M4 mAChR antagonist) via the i.c.v. route; and atropine > methoctramine > pirenzepine > tropicamide and 4‐DAMP via the i.t. route, respectively. OXO‐M injected via i.c.v. and i.t. had the same effects on BC, PT, MVP and VE as neostigmine by i.c.v. and i.t., respectively.CONCLUSIONS
These results indicate that activation of muscarinic cholinergic mechanisms by the cholinesterase inhibitor in the brain and spinal cord can inhibit the micturition reflex, mainly by affecting afferent pathways. These mAChR‐induced inhibitory effects seem to be mediated through M1/M3 receptor subtypes in the brain, while in the spinal cord, the M1/M2 receptor subtypes might be involved in inhibitory effects, which are mediated via inhibition of mechanoceptive C‐fibre afferent pathways. 相似文献16.
目的对麻醉恢复室(PACU)患者采用不同剂量新斯的明拮抗维库溴铵残余肌松阻滞(RNMB),观察能否缩短复苏时间及其理想剂量和效果。方法选择60例择期在气管内全麻下行胃肠手术的患者,术毕转入PACU后监测四个成串刺激比值(TOFR)来评定RNMB程度。当T1恢复至0.25时,患者随机分为N1,N3,N5和对照组N0组。N1,N3,N5组分别给予新斯的明10,30,50μg.kg-1和阿托品5,15,25μg.kg-1;对照组(N0组)静脉注射等容积生理盐水。分别记录注药后T1恢复至0.75的时间(恢复指数,RI)、TOFR恢复至0.7和0.9的时间、患者PACU留驻时间(T),以及病人给药后5 min内HR和BP变化并观察术后有无恶心呕吐的发生。结果不同剂量的新斯的明皆能明显加快RI和TOFR恢复至预定值的时间,并缩短PACU留驻时间(P<0.05)。与N1组比较,N3和N5组RNMB消除快,病人在PACU留驻时间缩短(P<0.05)。N5组较N3组RI和TOFR恢复至0.7的时间缩短(P<0.05)。术后各组病人恶心呕吐(PONV)发生率比较无统计学意义(P>0.05)。N3组、N5组在给药后1~2 min内HR明显加快(P<0.05),但MAP无明显变化(P>0.05);N0组与N1组的各时点HR和MAP比较差异不明显(P>0.05)。结论全麻术后转入PACU患者给予10~50μg.kg-1新斯的明合并5~25μg.kg-1阿托品均能有效拮抗维库溴铵的RNMB,并能有效缩短PACU留驻时间,且小剂量的新斯的明(10μg.kg-1)和阿托品(5μg.kg-1)联合应用对血流动力学干扰小。 相似文献
17.
新斯的明早期拮抗维库溴胺的可行性研究 总被引:1,自引:0,他引:1
目的 :探讨新斯的明早期拮抗维库溴胺的可行性。方法 :选择ASAⅠ~Ⅱ级 ,拟在全麻下行择期手术病人 48例 ,随机分成维库溴胺组 1 6例 ,维库溴胺 +新斯的明组 3 2例 ,后者又按在维库溴胺使用后不同时间内使用新斯的明分为Ⅰ、Ⅱ两组 ,1 0min内为Ⅰ (n=1 6例 ) ,在 1 1~3 0min内为Ⅱ (n =1 6例 )。麻醉开始后全部病人单次给予维库溴胺1 .5mg·kg-1,当手术结束时维库溴胺组静脉注入生理盐水 8ml,维库溴胺 +新斯的明组注入新斯的明0 .0 5mg·kg-1+阿托品 0 .0 2mg·kg-1+生理盐水至8ml。观察、记录各组病人从注入维库溴胺至肌张力恢复到四个成串刺激 (TOF) 0 .2 5、0 .70的时间。结果 :各组病人肌张力恢复至TOF 0 .2 5、0 .70时间为维库溴胺组 (4 5 .5 8± 8.88)min、(67.5 9±5 .60 )min。维库溴胺 +新斯的明组Ⅰ (2 3 .45±2 .82 )min、(3 1 .86± 3 .3 6)min。维库溴胺 +新斯的明组Ⅱ (2 8.70± 4.1 3 )min、(3 8.86± 2 .1 0 )min。维库溴胺 +新斯的明组恢复时间明显短于维库溴胺组(P <0 .0 1 ) ,维库溴胺 +新斯的明组Ⅰ恢复时间又明显短于维库溴胺 +新斯的明组Ⅱ (P <0 .0 1 )。手术后进行连续监测未发现再次阻滞现象。结论 :新斯的明可以早期拮抗维库溴胺的肌松效应 ,同时也提示拮抗时间愈早 ,肌张力 相似文献
18.
目的比较新斯的明、毒扁豆碱和毛果芸香碱对兔眼的缩瞳作用。方法18只家兔随机分为三组,用三种拟胆碱药水溶液滴眼,测量用药前后的瞳孔直径。结果滴眼后,三种药均在10min内出现缩瞳,0.5—1h内达最大效应,1.5—2.5h内逐渐减弱。药后50min内,毒扁豆碱的缩瞳效应优于新斯的明和毛果芸香碱,药后1—1.5h内,三者的作用无明显差异。新斯的明与毛果芸香碱的缩瞳作用相似。结论新斯的明、毒扁豆碱和毛果芸香碱滴眼给药,均能缩小兔眼瞳孔,其时效关系相似。 相似文献
19.
J Broad V W S Kung G Boundouki Q Aziz J H De Maeyer C H Knowles G J Sanger 《British journal of pharmacology》2013,170(6):1253-1261
BACKGROUND AND PURPOSE
Cholinesterase inhibitors such as neostigmine are used for acute colonic pseudo-obstruction, but cardio-bronchial side-effects limit use. To minimize side-effects, lower doses could be combined with a 5-HT4 receptor agonist, which also facilitates intestinal cholinergic activity. However, safety concerns, especially in the elderly, require drugs with good selectivity of action. These include the AChE inhibitor donepezil (used for Alzheimer''s disease, with reduced cardio-bronchial liability) and prucalopride, the first selective, clinically available 5-HT4 receptor agonist. This study examined their individual and potential synergistic activities in human colon.EXPERIMENTAL APPROACH
Neuronally mediated muscle contractions and relaxations of human colon were evoked by electrical field stimulation (EFS) and defined phenotypically as cholinergic, nitrergic or tachykinergic using pharmacological tools; the effects of drugs were determined as changes in ‘area under the curve’.KEY RESULTS
Prucalopride increased cholinergically mediated contractions (EC50 855 nM; 33% maximum increase), consistent with its ability to stimulate intestinal motility; donepezil (477%) and neostigmine (2326%) had greater efficacy. Concentrations of donepezil (30–100 nM) found in venous plasma after therapeutic doses had minimal ability to enhance cholinergic activity. However, donepezil (30 nM) together with prucalopride (3, 10 μM) markedly increased EFS-evoked contractions compared with prucalopride alone (P = 0.04). For example, the increases observed with donepezil and prucalopride 10 μM together or alone were, respectively, 105 ± 35%, 4 ± 6% and 35 ± 21% (n = 3–7, each concentration).CONCLUSIONS AND IMPLICATIONS
Potential synergy between prucalopride and donepezil activity calls for exploration of this combination as a safer, more effective treatment of colonic pseudo-obstruction. 相似文献20.
[目的]研究小茴香挥发油对在体小鼠胃肠运动及对家兔大鼠离体肠管收缩活动的影响。[方法] 1)小鼠在体实验:腹腔注射硫酸阿托品建立小鼠胃肠运动功能障碍模型,甲硫酸新斯的明腹腔注射建立小鼠胃排空和肠推进亢进模型,营养性半固体糊灌胃法观察小茴香挥发油对正常小鼠及上述两种模型小鼠小肠推进率和胃排空率的变化。2)离体肠道平滑肌实验:使用PowerLab15T生物信号采集系统观察小茴香挥发油对大鼠和家兔离体肠管运动的影响。[结果]小茴香挥发油不同浓度可以抑制正常小鼠的肠推进及甲硫酸新斯的明所致的肠推进亢进(P0.05);但对甲硫酸阿托品所致的小鼠胃肠运动抑制模型作用不明显,小茴香挥发油对大鼠和家兔离体小肠运动的频率和张力有极显著的抑制作用(P0.01)。[结论]小茴香挥发油具有抑制小鼠胃肠动力的作用,其作用机制可能是通过拮抗乙酰胆碱的作用,从而缓解胃肠道痉挛,为今后小茴香的制剂开发及临床用药的提供理论依据。 相似文献