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11.
慢性、持续的疼痛可能是患者就医最常见的原因,因此,临床上对慢性疼痛的治疗日益重视.然而,目前常用治疗疼痛的药物或手段由于存在各种缺陷,其治疗慢性疼痛的效果并不令人满意.为了寻找到新的更为有效的治疗疼痛的药物,人们花费了大量的精力深入研究疼痛的细胞和分子机制,N-甲基-D-天冬氨酸(N-methyl-D-aspartate, NMDA)受体在疼痛发生机制中作用的明确为疼痛新药的开发带来了希望.目前,不同类型的新镇痛药正在开发之中, 以NMDA受体为靶点,设法抑制NMDA受体的激活来治疗疼痛无疑成为研究的热点.本文简要介绍NMDA受体的结构及NMDA受体在疼痛发生机制中的作用,重点综述了抑制NMDA受体的激活来治疗慢性疼痛的研究进展. 相似文献
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Objective To investigate the sedative and hypnotic interaction between remifentanil and propofol by target-controlled infusion (TCI) during induction of anesthesia.Methods Third-two ASA Ⅰ or Ⅱpatients,aged 22-63 yr,body mass index 18-25 kg/m2,scheduled for elective surgery under general anesthesia,were randomly divided into 4 groups(n=8 each).Group Ⅰ only received TCI pmpofol.GroupⅡ,Ⅲ,and Ⅳreceived a target concentration of 2,4 or 6 ng/ml remifentanil respectively.While the blood-effect site concentrations of remifentanil were equilibrated,patients received TCI of propefol,with an initial target concentration of 0.5μg/ml.After the blood-effect site concentrations of propofol were equilibrated then with 0.5μg/ml increments until the loss consciousness was achieved.The eyelash reflex and state of consciousness were assessed and radial arterial blood sample 6 ml was taken every 3 min to determine the remifentanil and propofol concentrations in blood.Propofol and remifentanil concentrations in blood were measured by reversed-phase high-performance liquid chromatography and high-performance liquid chromatography with ultraviolet detection respectively.The sedative and hypnotic interaction between propofol and remifentanil was determined with a pharmacodynamie interaction model by regression analysis and determined using the isobolographic method.Results Propofol concentrations in blood were lower in group Ⅱ,Ⅲ and Ⅳ than group Ⅰ(P<0.05).The propofol concentratopms in blood were significantly decreased in trun with the increase in the remifentanil concentrations in blood in group Ⅱ-Ⅳ(P<0.05).At loss of eyelash reflex and loss of consciousness of patients,the pharmacodynamic interaction model by curve fitting was superior to linear regression (P<0.05).At loss of eyelash reflex of patients,the curve fitting result showed EC50,prop=2.77μg/ml and EC50,rem=26.67 ng/ml,and the isobolographic method equation is ECprop/2.77+ECrem/26.67=0.69.At loss of consciousness of patients,the curve fitting result showed EC50,prop==3.76μg/ml and EC50,rem=31.56ng/ml,and the isobolographic method equation is Ecprop/3.76+Ecrem/31.56=0.65.Conclusion Remifentanil (Cp 2-6 ng/ml) and propofol by TCI shows a synergistic type of pharmacodynamic interaction on the sedative and hypnotic during induction of anesthesia. 相似文献
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目的:探讨非体外静脉转流下原位肝移植手术中血管外肺水(EVLW)、肺血管通透性和死腔/潮气容积比(VD/VT)的变化及原因。方法:对15例晚期肝病行原位肝移植手术的患者行全身麻醉,术中全凭静脉靶控输注麻醉药维持,气管插管后经右颈内静脉和右股动脉放置PiCCO导管,通过PiCCO监护仪测定EVLW和肺血管通透性指数(PVPI),左桡动脉穿刺行动脉压监测和血气分析。分别记录手术开始30min(T1)、无肝期前15min(T2)、无肝期15min(T3)、无肝期45min(T4)、新肝期15min(T5)、新肝期60min(T6)、关腹(T7)时的EVLW、PVPI和动脉血气分析结果与呼气末二氧化碳浓度。结果:T4的EVLW明显低于T5,T3、T4的PVPI明显高于T5、T6和T7,T3、T4的VD/VT明显高于其他5个时刻。结论:非转流肝移植手术无肝期应当控制补液和EVLW,新肝期血管开放后可适当应用降低EVLW的药物,避免新肝期血管开放后引起肺水肿,无肝期的肺增血管通透性明显增高,有隐性肺损伤的可能,要注意采取适当的肺保护措施,无肝期的VD/VT高于其他两期,应当适当地减少通气量,以保持肺通气和血流的匹配。 相似文献
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脑功能区手术唤醒麻醉与清醒程度的研究 总被引:10,自引:2,他引:8
目的分析大脑功能区手术唤醒麻醉中对病人清醒程度的影响因素,提出脑功能区定位时态的概念.方法对15例病人采用丙泊酚靶控输注(TCI)给药,按作者提出的脑功能区定位时态评判标准对清醒程度进行评估.结果术中唤醒状态下语言清晰者10例,指令应答准确8例,无痛9例;颅内压正常10例.定位时态优5例,良8例,差2例.13例唤醒麻醉手术过程顺利,2例因脑组织膨胀未定位.结论丙泊酚TCI给药是脑功能区手术唤醒术较好的麻醉方法.应用脑功能区定位时态的概念对提高麻醉清醒质量有临床指导意义. 相似文献
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经尿道前列腺切除术并发严重低钠综合征一例 总被引:1,自引:0,他引:1
患者,男,64岁,ASAⅡ级,因进行性排尿困难1年余入院。术前诊断为前列腺Ⅲ度肥大并尿潴留,拟行经尿道前列腺电切术(TURP)。既往无高血压、心脏病等病史。术前检查:总蛋白58.2 g/L、尿素氮13.6 mmol/L、肌酐252μmol/L、尿酸525μmol/L、血Na 140mmol/L、Ca2 2.28mmol/L、K 4.84mmol/L。入室后BP 150/90mm Hg、HR 100次/min、SpO2 96%。常规连续硬膜外麻醉,L3-4穿刺,局麻药为1%利多卡因 0.15%丁卡因复合液,试验量为5ml,首次量为17ml,神经阻滞满意,平面为T10以下。手术开始后30min左右,患者出现 相似文献
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异丙酚预期浓度和双频指数对意识消失的预测概率比较 总被引:1,自引:0,他引:1
目的 比较预期血药浓度、效应室浓度和BIS等指标对意识消失预测概率 (Pk)。方法 选择ASAⅠ~Ⅱ级的择期手术患者 12例 ,以血药浓度为靶控目标浓度 ,预期血药浓度梯度为 0 5~ 1mg/L ,上下调整靶控目标浓度给予术中镇静 ,每一预期浓度维持 12min。双盲记录预期浓度、EEG参数、意识状态并计算各指标的意识消失的预测概率 ,比较预测概率的差异。结果 预期血药浓度、效应室浓度和BIS等指标预测意识消失的Pk 平均值分别为 :0 841,0 90 8和 0 817。效应室浓度与各指标的Pk 值之间差异有显著性 (P <0 0 5 )。结论 预期血药浓度、效应室浓度和BIS等指标均能用于预测意识消失和判断镇静深度 ,其中效应室浓度的预测价值最大。 相似文献
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目的 探讨水溶性脂聚体(WSLP)介导含2B亚基的N-甲基-D-天冬氨酸受体小干扰RNA(NR2B siRNA)治疗大鼠神经病理性痛的可行性.方法 健康雄性SD大鼠100只,周龄6周,体重180~200 g,采用随机数字表法,将大鼠随机分为5组(n=20):对照组(C组)、假手术组(S组)、神经病理性痛组(NP组)、WSLP-NR2B siRNA组(W组)、WSLP-阴性对照NR2B siRNA(WN组).采用坐骨神经分支部分结扎法制备大鼠神经病理性痛模型.C组不予任何处理;S组仅暴露坐骨神经,不牵拉和损伤神经;NP组于制备模型后即刻鞘内注射生理盐水20μl;W组和WN组于制备模型后即刻分别鞘内注射相应的siRNA 20μl.于模型制备前1 d及制备后3、7、14和21 d时测定机械缩足反应阈值(MWT)及热缩足反应持续时间(TWD),模型制备后3 d,痛阈测定结束后,每组取10只大鼠,取L4-6节段背根神经节,测定NR2B mRNA及其蛋白的表达水平.结果 与S组比较,NP组、W组和WN组MWT降低,TWD延长,NR2B mRNA及其蛋白表达上调(P<0.05或0.01),C组上述指标差异无统计学意义(P>0.05);与NP组比较,W组MWT升高,TWD缩短,NR2B mRNA及其蛋白表达下调(P<0.01),WN组上述指标差异无统计学意义(P>0.05).结论 WSLP不仅成功介导NR2B siRNA,抑制NR2B的表达,还可减轻大鼠神经病理性痛.Abstract: Objective To investigate the feasibility of NR2B small interference RNA(NR2B siRNA)carried by water-soluble lipopolymer(WSLP)for treatment of neuropathic pain in rats.Methods One hundred healthy male SD rats weighing 180-200 g were randomly divided into 5 groups(n=20 each):normal control group (group C),sham operation group(group S),neuropathic pain group(group NP),group WSLP-NR2B siRNA (group W)and group WSLP-negative NR2B siRNA(group WN).Neuropathic pain was induced by partial ligation of sciatic nenre.WSLP-NR2B siRNA complex was formed by binding WSLP and NR2B siRNA.Normal saline.WSLP-NR2B siRNA complex and WSLP-negative NR2B siRNA 20μl were injected intrathecally after operation in NP,W and WN groups respectively.Mechanical withdrawal threshold(MWT)and thermal withdrawal duration (TWD)were measured before(baseline)and at 3,7,14 and 21 days after operation.Ten animals in each group were sacrificed on the 3rd day after operation and the lumbar segment(L4-6)of the dorsal root ganglia was removed for determination of the expression of NR2B mRNA and protein using RT-PCR and Western blot analysis.Results Sciatic nerve ligation significantly decreased MWT and prolonged TWD and increased NR2B mRNA and protein expression in group NP as compared with group C.WSLP-NR2B siRNA complex significantly reduced sciatic nerve ligation-induced hyperalgesia and decreased NR2B mRNA and protein expression in group W as compared with group NP.Conclusion WSLP not only mediates NR2B siRNA successfully and inhibits the expression of NR2B,but also reduces neuropathic pain in rats. 相似文献