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1.
目的: 探讨水飞蓟宾(silybin,SB)对脂多糖(lipopolysaccharide,LPS)所致大鼠急性肾损伤的保护作用及机制。方法: 选用45只雄性SD大鼠,随机分为空白组(CTRL)、模型组(LPS)和水飞蓟宾给药组(LPS+SB)。LPS+SB组连续5 d灌胃给药(每日100 mg·kg-1),其他组采用等体积0.9%氯化钠溶液同步处理,第5天时LPS组与LPS+SB组灌胃给药2 h后腹腔注射LPS(10 mg·kg-1),CTRL组采用0.9%氯化钠溶液同步处理,8 h后经腹主动脉取血并收集肾脏组织;ELISA试剂盒检测血清、TNF-α和IL-6水平变化;生化试剂盒检测肌酐和尿素氮指标;HE染色观察肾组织病理学变化;Western blot法检测肾组织核转录因子-κB(NF-κB)、Nod样受体蛋白3(NLRP3)和相关蛋白的表达情况。结果: SB能够明显降低血清和组织中TNF-α和IL-6炎症因子水平,显著改善大鼠肾脏功能,减轻肾组织病理性损伤;Western blot结果表明SB可以抑制LPS所致NLRP3炎症相关蛋白的表达和NF-κB通路的激活。结论: SB可有效改善LPS所致大鼠肾损伤,作用机制可能与抑制NLRP3炎症小体激活以及调控NF-κB信号通路有关。 相似文献
2.
目的 探讨不同剂量抵挡汤对糖尿病小鼠心肌炎性病变的影响。方法 选取60只C57BL/6J小鼠,随机分为正常组(10只)和模型组(50只)。模型组小鼠采用高脂饲料联合链脲佐菌素(STZ)腹腔注射制备糖尿病小鼠模型,模型制备成功后继续高脂饲料喂养,8周后采用超声成像平台检测小鼠心功能,出现心功能减退,则糖尿病心肌病小鼠造模成功,剔除未成模小鼠,最终成模小鼠40只,模型组小鼠按照心功能随机分为模型组、抵挡汤低、中、高(1.5,3,6 g·kg-1)和辛伐他汀组(0.001 5 g·kg-1),每组8只。超声成像平台检测小鼠心功能,全自动生化仪检测小鼠空腹血糖(FBG),甘油三酯(TG),总胆固醇(TC),苏木素-伊红(HE)染色观察心肌组织病理学改变,蛋白免疫印迹法(Western blot)检测心肌组织NOD样受体3(NLRP3),硫氧还蛋白相互作用蛋白(TXNIP),半胱氨酸的天冬氨酸蛋白水解酶-1(Caspase-1),白细胞介素-1β(IL-1β)蛋白水平,检测心肌组织活性氧(ROS)含量。结果 与正常组比较,模型组的FBG,TC,TG的水平显著升高(P<0.01),左室射血分数(EF),左室短轴缩短率(FS)数值显著降低(P<0.01),ROS表达明显升高(P<0.05),心肌组织中NLRP3,TXNIP,Caspase-1,IL-1β表达明显升高(P<0.05)。与模型组比较,抵挡汤中、高剂量组及辛伐他汀组FBG,TC,TG水平明显降低(P<0.05);抵挡汤各剂量组及辛伐他汀组EF,FS均有改善(P<0.05),抵挡汤中剂量组变化更为明显(P<0.05);HE染色结果发现,抵挡汤能够改善小鼠心肌组织病理学变化;抵挡汤各剂量组及辛伐他汀组小鼠ROS表达水平明显减少,抵挡汤中剂量组变化更为明显;抵挡汤各剂量组NLRP3,TXNIP,Caspase-1,IL-1β表达明显降低,抵挡汤中剂量降低心肌组织NLRP3,TXNIP,Caspase-1表达的效果更为明显;抵挡汤高剂量降低心肌组织IL-1β表达的效果更为明显。结论 抵挡汤可通过抑制NLRP3炎症小体的激活,改善糖尿病心肌病小鼠心肌炎性病变。 相似文献
3.
4.
探讨连续血液净化(CBP)对脓毒症患者外周血核苷酸结合寡聚化受体蛋白3(NLRP3)及肠道屏障功能的影响。方法 选取2019年5月~2021年5月新疆医科大学第一附属医院重症医学中心收治的脓毒症及非脓毒症患者83例。在镇痛、镇静、液体复苏、抗感染等治疗基础上,根据治疗方式不同,分为脓毒症CBP治疗组(n=24)、脓毒症常规治疗组(n=35)、非脓毒症组(n=24例)。收集各组患者在入住ICU后的一般资料、基础疾病、感染部位、炎症因子水平、肌酐、急性胃肠损伤(AGI)评分、APACHEⅡ评分、28 d预后等资料并进行回顾性分析。结果 3组患者的性别、基础疾病、感染部位等比较差异无统计学意义(P>0.05),CBP治疗组患者基线期APACHEⅡ评分高于其余两组(P<0.05)。与上机前相比,脓毒症CBP治疗组在上机3天后的乳酸、血浆尿素氮(BUN)、外周血淋巴细胞中NF-κB p65、Caspase-1、ASC,血清中IL-1β 、IL-18、血清肠型脂肪酸结合蛋白(I-FABP)、AGI评分有显著降低(均P<0.05)。 脓毒症CBP治疗组28 d死亡率为70.83%,明显高于脓毒症常规治疗组(28.57%)及非脓毒症组(16.67%),差异具有统计学意义(P<0.05)。结论 血液净化治疗可减少脓毒症患者外周血淋巴细胞中 NLRP3 炎症小体的活化,继而减少体内炎症因子水平,改善胃肠道屏障功能。 相似文献
5.
目的探讨海水吸入型急性肺损伤大鼠肺组织中NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎症小体表达的变化及介导的炎性因子在急性肺损伤(ALI)发生发展中的作用。 方法将50只健康雄性SD大鼠随机分为5组,对照组,海水吸入1 h组,海水吸入3 h组,海水吸入6 h组,海水吸入9 h组,每组10只。采用经气管缓慢滴注(3 ml/kg)海水的方法制作大鼠损伤模型。制作大鼠肺脏石蜡切片并HE染色观察病理形态学变化。检测大鼠肺组织湿干比。ELISA检测测定各组肺组织中IL-1β和IL-18水平,RT-PCR检测肺组织中IL-1β、IL-18和NLRP3mRNA的表达。Western-blot检测肺组织中NLRP3蛋白表达。 结果气管滴注海水后成功复制海水吸入性急性肺损伤模型。肺组织湿干比较对照组显著升高。病理形态学观察可见肺组织大量炎细胞浸润、水肿、间质增厚。各组大鼠血清中IL-1β和IL-18的水平随着时间增加逐渐升高,且在3~6 h达到顶峰,随后炎症因子的表达逐渐降低。与空白对照组比较,差异均有统计学意义(均P<0.05)。各组大鼠肺组织中IL-1β和IL-18的mRNA的表达水平与大鼠肺组织中IL-1β和IL-18的表达基本一致。与空白对照组比较,差异均有统计学意义(均P<0.05)。肺组织匀浆中NLRP3转录和翻译结果显示海水吸入刺激后,肺组织中NLRP3的mRNA和NLRP3蛋白含量变化含量随着时间明显逐渐增加,差异均有统计学意义(均P<0.05)。 结论海水刺激下,NLRP3炎症小体介导的炎症反应参与了急性肺损伤发病过程并加重了肺损伤的程度,可能是海水急性肺损伤的发病机制之一,但其作用有待进一步证实。 相似文献
6.
Ghrelin, a brain-gut peptide, has been proven to exert neuroprotection in different kinds of neurological diseases; however, its role and the potential molecular mechanisms in secondary brain injury (SBI) after intracerebral hemorrhage (ICH) are still unknown. In this study, we investigate whether treatment with ghrelin may attenuate SBI in a murine ICH model, and if so, whether the neuroprotective effects are due to the inhibition of nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation and promotion of nuclear factor-E2-related factor 2 (Nrf2)/antioxidative response element (ARE) signaling pathway. Stereotactically intrastriatal infusion of autologous blood was performed to mimic ICH. Ghrelin was given intraperitoneally immediately following ICH and again 1 h later. Results showed that ghrelin attenuated neurobehavioral deficits, brain edema, hematoma volume, and perihematomal cell death post-ICH. Ghrelin inhibited the NLRP3 inflammasome activation and subsequently suppressed the neuroinflammatory response as evidenced by reduced microglia activation, neutrophil infiltration, and pro-inflammatory mediators release after ICH. Additionally, ghrelin alleviated ICH-induced oxidative stress according to the chemiluminescence of luminol and lucigenin, malondialdehyde (MDA) content, and total superoxide dismutase (SOD) activity assays. These changes were accompanied by upregulation of Nrf2 expression, Nrf2 nuclear accumulation, and enhanced Nrf2 DNA binding activity, as well as by increased expressions of Nrf2 downstream target antioxidative genes, including NAD(P)H quinine oxidoreductase-1 (NQO1), glutathione cysteine ligase regulatory subunit (GCLC), and glutathione cysteine ligase modulatory subunit (GCLM). Together, our data suggested that ghrelin protected against ICH-induced SBI by inhibiting NLRP3 inflammasome activation and promoting Nrf2/ARE signaling pathway. 相似文献
7.
Neuroinflammation plays an active role in the pathogenesis of several neurodegenerative diseases, including Parkinson’s disease (PD). Earlier studies from this laboratory showed that glia maturation factor (GMF), a proinflammatory mediator; is up-regulated in the brain in neurodegenerative diseases and that deficiency of GMF showed decreased production of IL-1β and improved behavioral abnormalities in mouse model of PD. However, the mechanisms linking GMF and dopaminergic neuronal death have not been completely explored. In the present study, we have investigated the expression of NLRP3 inflammasome and caspase-1 in the substantia nigra (SN) of human PD and non-PD brains by immunohistochemistry. Wild-type (WT) and GMF−/− (GMF knock-out) mice were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP) and the brains were isolated for neurochemical and morphological examinations. NLRP3 and caspase-1 positive cells were found significantly increased in PD when compared to non-PD control brains. Moreover, GMF co-localized with α-Synuclein within reactive astrocytes in the midbrain of PD. Mice treated with MPTP exhibit glial activation-induced inflammation, and nigrostriatal dopaminergic neurodegeneration. Interestingly, increased expression of the inflammasome components in astrocytes and microglia observed in the SN of MPTP-treated WT mice were significantly reduced in GMF−/− mice. Additionally, we show that NLRP3 activation in microglia leads to translocation of GMF and NLRP3 to the mitochondria. We conclude that downregulation of GMF may have beneficial effects in prevention of PD by modulating the cytotoxic functions of microglia and astrocytes through reduced activation of the NLRP3 inflammasome; a major contributor of neuroinflammation in the CNS. 相似文献
8.
Tomonori Suzuki Kuniko Kohyama Kengo Moriyama Mariko Ozaki Setsuko Hasegawa Taro Ueno Minoru Saitoe Tomohiro Morio Masaharu Hayashi Hiroshi Sakuma 《European journal of immunology》2020,50(2):205-219
The NLRP3 inflammasome is a molecular complex that translates signals from pathogens and tissue damage into inflammatory responses, and plays crucial roles in numerous neurological diseases. Activation of the NLRP3 inflammasome leads to caspase-1 dependent cleavage of pro-IL-1β to form mature IL-1β. By acting on the P2X7 purinergic receptor, extracellular ATP is one of the major stimuli that activates the NLRP3 inflammasome. Although microglia express multiple purinergic receptors, their roles in inflammasome-mediated inflammation are largely unknown. We studied the role of the P2Y12 receptor, a metabotropic P2Y receptor enriched in microglia, on inflammation in vitro. Inhibition of the microglial P2Y12 receptor by PSB0739 or siRNA knockdown suppressed IL-1β release. P2Y12 receptor-deficient microglia displayed markedly attenuated IL-1β mRNA expression and release. P2Y12 receptor blockade also suppressed IL-6 production. Both IL-1β and IL-6 responses were augmented by extracellular ADP or ADP-βS and were abrogated by PSB0739. Mechanistically, ADP-βS potentiated NF-κB activation. In addition, ADP altered mitochondrial membrane potential in combination with ATP and increased the number of caspase-1 positive cells through the P2Y12 receptor. These results elucidate a novel inflammatory mechanism by which extracellular ADP acts on the P2Y12 receptor to activate NF-κB and the NLRP3 inflammasome to enhance microglial inflammation. 相似文献
9.
探讨胆囊结石与胆囊组织IL1-SymbolbA@表达及其成熟分泌的相关性。
〖HT5”H〗方法〖HT5”K〗〓收集胆结石胆囊及其胆汁样本21例,其中胆固醇结石4例、色素结石7例、混合结石10例,采用PCR检测细菌感染情况,ELISA检测胆汁中IL1-SymbolbA@,
蛋白印迹杂交方法检测IL1-SymbolbA@蛋白表达,免疫组化检测胆囊黏膜IL1-SymbolbA@表达,并分析临床相关性。结果在排除伴有细菌感染的情况下,
结石患者胆汁IL1-SymbolbA@含量在1.93~11.80ng/ml,混合结石组胆汁IL1-SymbolbA@(4.753±2.651)显著高于胆固醇结石组(2.640±0.167)和色素结石组(2.762±1.081)
(P<0.05);免疫组化、蛋白印迹杂交检测表明胆囊黏膜proIL1-SymbolbA@、IL1-SymbolbA@高表达,推测是胆汁IL1-SymbolbA@重要来源之一、
并示胆结石患者胆囊黏膜有炎症小体激活。结论胆结石患者在非细菌感染情况下,胆汁IL1-SymbolbA@增加可能与胆囊黏膜细胞炎症小体的激活密切相关。 相似文献
10.
Viroporins are a group of low-molecular-weight proteins containing about 50–120 amino acid residues, which are encoded by animal viruses. Viroporins are involved in several stages of the viral life cycle, including viral gene replication and assembly, as well as viral particle entry and release. Viroporins also play an important role in the regulation of antiviral innate immune responses, especially in inflammasome formation and activation, to ensure the completion of the viral life cycle. By reviewing the research progress made in recent years on the regulation of the NLRP3 inflammasome by viroporins of animal viruses, we aim to understand the importance of viroporins in viral infection and to provide a reference for further research and development of novel antiviral drugs. 相似文献