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排序方式: 共有637条查询结果,搜索用时 15 毫秒
91.
Danielle M. Hurzy Darrell A. Henze Tamara D. Cabalu Kartik Narayan Amanda Heller Andrew J. Cooke 《Bioorganic & medicinal chemistry letters》2017,27(12):2695-2701
A series of substituted indoles were examined as selective inhibitors of tropomyosin-related kinase receptor A (TrkA), a therapeutic target for the treatment of pain. An SAR optimization campaign based on ALIS screening lead compound 1 is reported. 相似文献
92.
Wentao Wu Zhixiang Li Guangwen Yang Mingxing Teng Jian Qin Zhijing Hu Lijuan Hou Liang Shen Haiheng Dong Yang Zhang Jian Li Shuhui Chen Jingwei Tian Jianzhao Zhang Liang Ye 《Bioorganic & medicinal chemistry letters》2017,27(10):2210-2215
hNav1.7 small molecular inhibitors have attracted lots of attention by its unique analgesic effect. Herein, we report the design and synthesis of a novel series of tetrahydropyridine analogs as hNav1.7 inhibitors for analgesia. Detail structural–activity relationship (SAR) studies were undertaken towards improving hNav1.7 activity, in vitro ADME, and in vivo PK profiles. These efforts resulted in the identification of compound (?)-15h, a highly potent and selective hNav1.7 inhibitor with good ADME and PK profiles. 相似文献
93.
Yoshiyuki Okumura Tatsuya Yamagishi Seiji Nukui Kazunari Nakao 《Bioorganic & medicinal chemistry letters》2017,27(5):1186-1192
Starting from acylsufonamide HTS hit 2, a novel series of para-N-acylaminomethylbenzoic acids was identified and developed as selective prostaglandin EP4 receptor antagonists. Structural modifications on lead compound 4a were explored with the aim of improving potency, physicochemical properties, and animal PK predictive of QD (once a day) dosing regimen in human. These efforts led to the discovery of the clinical candidate AAT-008 (4j), which exhibited significantly improved pharmacological profiles over grapiprant (1). 相似文献
94.
Mingxing Teng Wentao Wu Zhixiang Li Guangwen Yang Jian Qin Yikai Wang Zhijing Hu Haiheng Dong Lijuan Hou Guoping Hu Liang Shen Yang Zhang Jian Li Shuhui Chen Jingwei Tian Liang Ye Jianzhao Zhang Hongbo Wang 《Bioorganic & medicinal chemistry letters》2017,27(22):4979-4984
hNav1.7 receives a lot of attention owing to its attractive mechanism of action in pain processing pathway. We have previously reported our design of a novel series of tetrahydropyridine analogues towards hNav1.7 selective inhibitors. Herein, we disclose further efforts to the optimization of hit compound (?)-6, which led to the identification of aminocyclohexene analogues (?)-9 and (?)-17 with good potency, high selectivity, and minimal CYP inhibition. Both compounds (?)-9 and (?)-17 demonstrated improved pharmacokinetic profiles in rats, and robust efficacy in rat formalin-induced nociception and spinal nerve ligation (SNL) models. 相似文献
95.
Lipopolysaccharide (LPS) has been used extensively to study neuroinflammation, but usually its effects were examined acutely (24 h<). We have shown previously that a single intraperitoneal LPS injection activated satellite glial cells (SGCs) in mouse dorsal root ganglia (DRG) and altered several functional parameters in these cells for at least one week. Here we asked whether the LPS effects would persist for 1 month. We injected mice with a single LPS dose and tested pain behavior, assessed SGCs activation in DRG using glial fibrillary acidic protein (GFAP) immunostaining, and injected a fluorescent dye intracellularly to study intercellular coupling. Electron microscopy was used to quantitate changes in gap junctions. We found that at 30 days post-LPS the threshold to mechanical stimulation was lower than in controls. GFAP expression, as well as the magnitude of dye coupling among SGCs were greater than in controls. Electron microscopy analysis supported these results, showing a greater number of gap junctions and an abnormal growth of SGC processes. These changes were significant, but less prominent than at 7 days post-LPS. We conclude that a single LPS injection exerts long-term behavioral and cellular changes. The results are consistent with the idea that SGC activation contributes to hyperalgesia. 相似文献
96.
目的:探讨右美托咪定对腰椎全麻手术患者术后疼痛及认知功能的影响。方法:选择2014年3月~2015年12月在我院行腰椎全麻手术的84例患者为研究对象,按照随机数字表法分为对照组(42例)和试验组(42例),患者均常规给予芬太尼及顺式阿曲库铵麻醉诱导,试验组患者在麻醉诱导过程中给予右美托咪定静脉注射,对照组患者仅给予氯化钠注射液静脉注射。分别于术前(T0)、手术开始2 h(T2)、术后24 h(T24)检测血清肾上腺糖皮质激素,采用疼痛视觉模拟评分法(VAS)进行疼痛评定;采用简易智能精神状态量表(MMSE)于术后1d和2d进行认知状态评定,并计算术后认知功能障碍(POCD)发生率;同时观察患者不良反应发生情况。结果:试验组患者T2和T24时肾上腺糖皮质激素水平明显低于T0,T2时试验组患者肾上腺糖皮质激素水平明显低于对照组,差异有统计学意义(P0.05)。试验组患者T2时VAS评分明显低于对照组,差异有统计学意义(P0.05)。术后1d和2d时试验组患者的MMSE评分高于对照组,POCD发生率明显低于对照组;两组患者术后2d时MMSE评分高于术后1d,POCD发生率明显低于术后1d,差异均有统计学意义(P0.05)。两组患者均未见除POCD以外的不良反应。结论:右美托咪定有较强的抗氧化能力,可有效减轻腰椎全麻手术患者的疼痛程度,提高患者的认知功能。 相似文献
97.
目的:研究依托咪酯持续输注用于乳腺癌根治术患者的镇痛效果及对血流动力学与炎症介质的影响。方法:选取2015年8月至2016年7月我院收治的84例乳腺癌根治术患者,根据患者入院顺序分为观察组和对照组,42例每组。观察组持续输注依托咪酯,对照组持续输注丙泊酚。比较两组患者手术后不同时点视觉模拟评分(VAS),拔管时舒张压(DBP)、收缩压(SBP)、心率(HR)及血清白介素-2(IL-2)、IL-10、IL-12水平的变化。结果:拔管时,观察组的DBP、SBP、HR水平显著低于对照组(P0.05)。观察组在术后1、5、10、24、48 h的VAS评分均显著低于对照组(P0.05)。观察组术后3天时血清IL-2水平显著高于对照组(P0.05),IL-10、IL-12水平显著低于对照组(P0.05)。结论:依托咪酯持续输注用于乳腺癌根治术患者中的镇痛效果良好,且对患者血流动力学与炎症反应的影响较小。 相似文献
98.
目的:探讨腰椎旁神经阻滞联合超短波对腰椎间盘突出症疼痛及腰背肌生物力学性能的影响。方法:选择我院2014年2月~2016年8月收治的98例腰椎间盘突出症患者,按抽签法分组对照组与研究组。对照组采用腰椎旁神经阻滞治疗,研究组基于对照组加用超短波治疗。观察两组的临床疗效、治疗前后视觉模拟评分(VAS)、60°/s角速、120°/s角速平均功率(AP)、峰力矩(PT)、腰背屈/伸比值(F/E)、血清P物质(SP)、β-内啡肽(β-EP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平的变化及不良反应的发生情况。结果:研究组总有效率为95.91%,显著高于对照组,差异有统计学意义(P0.05)。治疗后,两组F/E值、血清SP、IL-6、TNF-α水平均较治疗前显著降低,且研究组以上指标均明显低于对照组,两组AP、PT、血清β-EP水平均较治疗前明显上升,且研究组以上指标显著高于对照组,差异均有统计学意义(P0.05)。两组不良反应的发生率比较差异无统计学意义(P0.05)。结论:腰椎旁神经阻滞联合超短波治疗腰椎间盘突出症的效果明显优于单用腰椎旁神经阻滞治疗,其可有效缓解疼痛及改善腰背肌生物力学性能,并减轻炎症反应。 相似文献
99.
Pain is unfortunately a quite common symptom for cancer patients. Normally pain starts as an episodic experience at early cancer phases to become chronic in later stages. In order to improve the quality of life of oncological patients, anti-cancer treatments are often accompanied by analgesic therapies. The P2X receptor are adenosine triphosphate (ATP) gated ion channels expressed by several cells including neurons, cancer and immune cells. Purinergic signaling through P2X receptors recently emerged as possible common pathway for cancer onset/growth and pain sensitivity. Indeed, tumor microenvironment is rich in extracellular ATP, which has a role in both tumor development and pain sensation. The study of the different mechanisms by which P2X receptors favor cancer progression and relative pain, represents an interesting challenge to design integrated therapeutic strategies for oncological patients. This review summarizes recent findings linking P2X receptors and ATP to cancer growth, progression and related pain. Special attention has been paid to the role of P2X2, P2X3, P2X4 and P2X7 in the genesis of cancer pain and to the function of P2X7 in tumor growth and metastasis. Therapeutic implications of the administration of different P2X receptor blockers to alleviate cancer-associated pain sensations contemporarily reducing tumor progression are also discussed. 相似文献
100.
Locomotor Dysfunction and Pain: The Scylla and Charybdis of Fiber Sprouting After Spinal Cord Injury 总被引:1,自引:0,他引:1
Injury to the spinal cord (SCI) can produce a constellation of problems including chronic pain, autonomic dysreflexia, and motor dysfunction. Neuroplasticity in the form of fiber sprouting or the lack thereof is an important phenomenon that can contribute to the deleterious effects of SCI. Aberrant sprouting of primary afferent fibers and synaptogenesis within incorrect dorsal horn laminae leads to the development and maintenance of chronic pain as well as autonomic dysreflexia. At the same time, interruption of connections between supraspinal motor control centers and spinal cord output cells, due to lack of successful regenerative sprouting of injured descending fiber tracts, contributes to motor deficits. Similarities in the molecular control of axonal growth of motor and sensory fibers have made the development of cogent therapies difficult. In this study, we discuss recent findings related to the degradation of inhibitory barriers and promotion of sprouting of motor fibers as a strategy for the restoration of motor function and note that this may induce primary afferent fiber sprouting that can contribute to chronic pain. We highlight the importance of careful attentiveness to off-target molecular- and circuit-level modulation of nociceptive processing while moving forward with the development of therapies that will restore motor function after SCI. 相似文献