全文获取类型
收费全文 | 5103篇 |
免费 | 213篇 |
国内免费 | 136篇 |
专业分类
耳鼻咽喉 | 9篇 |
儿科学 | 58篇 |
妇产科学 | 61篇 |
基础医学 | 1177篇 |
口腔科学 | 43篇 |
临床医学 | 299篇 |
内科学 | 662篇 |
皮肤病学 | 89篇 |
神经病学 | 266篇 |
特种医学 | 132篇 |
外国民族医学 | 4篇 |
外科学 | 150篇 |
综合类 | 583篇 |
预防医学 | 349篇 |
眼科学 | 71篇 |
药学 | 981篇 |
3篇 | |
中国医学 | 280篇 |
肿瘤学 | 235篇 |
出版年
2023年 | 81篇 |
2022年 | 104篇 |
2021年 | 181篇 |
2020年 | 224篇 |
2019年 | 150篇 |
2018年 | 127篇 |
2017年 | 190篇 |
2016年 | 214篇 |
2015年 | 162篇 |
2014年 | 424篇 |
2013年 | 664篇 |
2012年 | 467篇 |
2011年 | 475篇 |
2010年 | 336篇 |
2009年 | 281篇 |
2008年 | 251篇 |
2007年 | 135篇 |
2006年 | 106篇 |
2005年 | 115篇 |
2004年 | 101篇 |
2003年 | 66篇 |
2002年 | 47篇 |
2001年 | 14篇 |
2000年 | 7篇 |
1999年 | 7篇 |
1998年 | 20篇 |
1997年 | 17篇 |
1996年 | 14篇 |
1995年 | 8篇 |
1994年 | 5篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 74篇 |
1984年 | 64篇 |
1983年 | 60篇 |
1982年 | 61篇 |
1981年 | 48篇 |
1980年 | 45篇 |
1979年 | 46篇 |
1978年 | 25篇 |
1977年 | 7篇 |
1976年 | 5篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1972年 | 1篇 |
排序方式: 共有5452条查询结果,搜索用时 906 毫秒
101.
Innate immune system plays a critical role in determining the progression and severity of acetaminophen hepatotoxicity 总被引:8,自引:0,他引:8
BACKGROUND & AIMS: Inflammatory mediators released by nonparenchymal inflammatory cells in the liver have been implicated in the progression of acetaminophen (APAP) hepatotoxicity. Among hepatic nonparenchymal inflammatory cells, we examined the role of the abundant natural killer (NK) cells and NK cells with T-cell receptors (NKT cells) in APAP-induced liver injury. METHODS: C57BL/6 mice were administered a toxic dose of APAP intraperitoneally to cause liver injury with or without depletion of NK and NKT cells by anti-NK1.1 monoclonal antibody (MAb). Serum alanine transaminase (ALT) levels, liver histology, hepatic leukocyte accumulation, and cytokine/chemokine expression were assessed. RESULTS: Compared with APAP-treated control mice, depletion of both NK and NKT cells by anti-NK1.1 significantly protected mice from APAP-induced liver injury, as evidenced by decreased serum ALT level, improved survival of mice, decreased hepatic necrosis, inhibition of messenger RNA (mRNA) expression for interferon-gamma (IFN-gamma), Fas ligand (FasL), and chemokines including KC (Keratinocyte-derived chemokine); MIP-1 alpha (macrophage inflammatory protein-1 alpha); MCP-1 (monocyte chemoattractant protein-1); IP-10 (interferon-inducible protein); Mig (monokine induced by IFN-gamma) and decreased neutrophil accumulation in the liver. Hepatic NK and NKT cells were identified as the major source of IFN-gamma by intracellular cytokine staining. APAP induced much less liver injury in Fas-deficient (lpr) and FasL-deficient (gld) mice compared with that in wild-type mice. CONCLUSIONS: NK and NKT cells play a critical role in the progression of APAP-induced liver injury by secreting IFN-gamma, modulating chemokine production and accumulation of neutrophils, and up-regulating FasL expression in the liver, all of which may promote the inflammatory response of liver innate immune system, thus contributing to the severity and progression of liver injury downstream of the metabolism of APAP and depletion of reduced glutathione (GSH) in hepatocytes. 相似文献
102.
目的:研究慢性阻塞性肺疾病(COPD)大鼠血浆、肺、心、肝、和肾组织中氧化/抗氧化水平,及γ谷氨酰半胱氨酸合成酶(γ-GCS)活性及其表达在各器官组织中的差异和变化。方法:健康雄性Wistar大鼠14只,随机分COPD模型组和对照组,每组7只。采用每日熏香烟和两次气管内滴入脂多糖(LPS)法制作COPD大鼠模型。检测大鼠血浆、肺、心、肝和肾组织中还原型谷胱甘肽(GSH)、活性氧(ROS)、总抗氧化力(T-AOC)和γ-GCS活性。用逆转录-聚合酶链反应(RT-PCR)法检测肺、心、肝和肾组织中γ-GCS mRNA的表达。结果:COPD组大鼠心、肝中GSH、ROS、T-AOC和γ-GCS活性均显著增高(P均<0.05),但未显示出明显氧化/抗氧化失衡。肺中GSH和ROS提高,而T-AOC下降明显(P均<0.05),表明提高的GSH不足以抵御氧化作用,明显存在氧化/抗氧化失衡。血清中ROS增高,GSH和T-AOC下降明显,显示系统性氧化/抗氧化失衡。COPD大鼠肺组织γ-GCS mRNA表达较对照组显著增高(P<0.05),而心、肝、肾组织中γ-GCS mRNA表达与对照组无明显差异(P>0.05)。结论:COPD大鼠肺内存在氧化/抗氧化失衡,肺组织是γ-GCS表达的主要部位,在抗氧化损伤中可能发挥重要作用。 相似文献
103.
104.
芹菜素γ-环糊精包合物的表征和抗氧化活性研究 总被引:1,自引:0,他引:1
目的研究芹菜素与γ-环糊精(γ-CD)包合物的制备、表征、包合机制及其抗氧化活性。方法采用加热回流共沉淀法制备芹菜素γ-环糊精包合物,红外光谱法(IR)对形成的包合物进行表征,荧光光谱法测定包合物的包合常数(K)和包合比(n);荧光光谱法和核磁共振法(NMR)研究芹菜素与γ-CD在溶液中形成的包合物;双倒数曲线法研究包合前后对自由基1,1-二苯基-2-三硝基苯肼(DPPH·)的清除率。结果在不同的pH值溶液中,γ-CD对芹菜素具有不同的包合能力,γ-CD最适合在中性介质中与芹菜素形成包合物,在实验浓度范围内按1∶1形成包合物,包合比为1236,包合物对自由基DPPH·的清除活性更强;NMR确定包合物的结构。结论在实验条件下,芹菜素分子从γ-CD大口端进入到空腔内形成稳定的包合物,且抗氧化活性增加。 相似文献
105.
ObjectiveThe study was aimed to explore the hepatocellular protective functions of cafestol during hepatic ischemia-reperfusion injury and the possible mechanisms.MethodsNinety male Balb/c mice were randomly divided into seven groups, including normal control group, L-cafestol(20mg/kg) group, H-cafestol(40mg/kg) group, sham group, IR group, L-cafestol(20mg/kg) + IR group, H-cafestol(40mg/kg) + IR group. Serum liver enzymes (ALT, AST), inflammation mediators, proteins associated with apoptosis and autophagy, indicators linked with ERK/PPARγ pathway, and liver histopathology were measured using ELISA, qRT-PCR, immunohistochemical staining, and western blotting at 2, 8, and 24 hours after reperfusion.ResultsOur findings confirmed that cafestol preconditioning groups could reduce the levels of ALT and AST, alleviate liver pathological damage, suppress the release of inflammation mediators, inhibit the production of pro-apoptosis protein including caspase-3, caspase-9 and Bax, decrease the expression of autophagy-linked protein including Beclin-1 and LC3, increase anti-apoptosis protein Bcl-2, and restrain the activation of ERK and PPARγ.ConclusionCafestol preconditioning could attenuate inflammatory response, apoptosis and autophagy on hepatic ischemia reperfusion injury by suppressing ERK/PPARγ pathway. 相似文献
106.
Tijana Subotički Olivera Mitrović Ajtić Mileva Mićić Tamara Kravić Stevović Dragoslava Đikić Miloš Diklić 《Ultrastructural pathology》2013,37(6):498-507
In accordance with increased proliferation in myeloproliferative neoplasm (MPN), the goal is to evaluate the immunoexpression of: β-catenin, PPAR-γ and Ki67 protein, to compare them with bone marrow ultrastructural characteristics in patients with MPN. Immunoexpression and electron microscopy of bone marrow was analyzed in 30 Ph-negative MPN patients, including per 10 patients with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The quantity of β-catenin immunoreactive cells was significantly higher in PV then in ET (p < 0.01) or PMF group of patients (p < 0.01) and also in ET versus PMF group of patients (p < 0.01). Erythroid lineage showed absent β-catenin staining without immunoreactivity in nucleus. In contrast, immunoreactivity for PPAR-γ was localized mostly in megakaryocytes and the highest number of PPAR-γ immunopositive cells was detected in PMF group of patients. In addition, the proliferative Ki67 index was significantly increased in the PMF and PV patients compared to patients with ET. Also, the megakaryocytes showed abnormal maturation in PMF group of patients as determined by ultrastructural analysis. These results indicated that PV dominantly expressed β-catenin and proliferation marker Ki67 in bone marrow, while PMF is linked preferentially to PPAR-γ immunopositive megakaryocytes characterized by abnormal maturation. 相似文献
107.
Yuh-Cheng Yang Tzu-Yang Chang Tze-Chien Chen Shih-Chuan Chang Wen-Shan Lin Yann-Jinn Lee 《Human immunology》2013
Cervical cancer is strongly associated with infection of oncogenic types of human papillomavirus (HPV). However, HPV infection alone is not sufficient for progression to cervical cancer. It is now recognized that host immunogenetic background participates in the control of HPV infection and development of cervical cancer. Interleukin-18 (IL-18) is a multifunctional cytokine that induces interferon-gamma secretion and plays a central role in antitumor immunity. The aim of this study is to determine if potentially functional polymorphisms in IL-18 gene are associated with risk of HPV-induced cervical cancer in Taiwanese women. Pre-Developed TaqMan Allelic Discrimination Assay was used to genotype IL-18 −1297 T/C, −607 C/A, −380 C/G, −137 G/C, and +105 A/C polymorphisms in a hospital-based study of 470 women with cervical squamous cell carcinoma (CSCC) and 722 age-matched healthy control women. The presence and genotypes of HPV in CSCC was determined by PCR. None of the polymorphisms or any haplotype was found to have significant differences in distribution among all subjects with CSCC, those with HPV-16 positive CSCC, and controls. Our results suggest that the IL-18 −1297 T/C, −607 C/A, −380 C/G, −137 G/C, and +105 A/C polymorphisms are not associated with susceptibility to CSCC in Taiwanese women. 相似文献
108.
目的 探讨灵芝多糖(GLP)对外周血淋巴细胞免疫分群的影响及其作用机制.方法 取肿瘤患者和正常人的外周血,分离外周血单个核细胞(PBMC)后,用不同剂量的GLP(10 ng/ml、50ng/ml和100 ng/ml)刺激后,用流式细胞仪检测DC细胞表面分子(HLA-DR、CD83和CD11c)、Th1细胞、Th2细胞和NK(CD3-CD56+)细胞数;并进一步用免疫磁珠分选出正常人外周血CD4+ Th细胞后用不同浓度GLP刺激24h后,荧光实时定量Q-PCR检测Th1和Th2细胞因子的表达水平,Westernblot分析Th1分化相关的转录因子水平.结果 灵芝多糖可以在体外呈浓度依赖性增加外周血中Th1细胞亚群和DC共刺激分子的表达(P<0.01),并且增加STAT4的表达和IL-12、IFN-γ和TNF-α的mRNA的表达水平(P<0.01).结论 灵芝多糖可能通过增加Th细胞STAT4的表达水平,促进其向Th1细胞分化,并增加Th1的分泌细胞因子. 相似文献
109.
目的对比分析轻症和重症甲型H1 N1流感患者的细胞免疫学特征,为该病的病情监测和治疗提供科学依据。方法收集2009年7月1日至2009年12月31日于宁波市第二医院及宁海县第一医院就诊并确诊为甲型H1N1流感的204名患者作为病例组,其中轻症组52例,重症组152例,选取同时期的26名健康志愿者作为对照组;采用流式细胞仪检测各组外周血淋巴细胞亚群,采用ELISA方法检测各组血清干扰素-γ(IFN-γ)及白细胞介素-4(IL-4)水平。结果 H1N1流感患者重症组外周血淋巴细胞计数降低显著,与健康对照组及轻症组患者比较差异均有统计学意义(P<0.01);重症组T淋巴细胞、NK细胞、CD4+T及CD8+T淋巴细胞计数、百分比均较轻症组显著降低( P<0.01),B淋巴细胞及CD4+T/CD8+T比值虽然较轻症组降低,但差异无统计学意义(P=0.11,0.175);轻症组和重症组血清IFN-γ水平均较健康对照组降低,但是重症组降低更为显著(与健康对照组和轻症组比较,P<0.01);同样,轻症组和重症组血清IL-4水平均较健康对照组降低,但各组间比较统计学差异均无显著性意义(P>0.05)。结论甲型H1N1流感患者免疫功能的异常与病情轻重有一定关系,尤其是细胞免疫功能,监测患者的免疫功能变化,对于判断患者的病情有较好的参考价值。 相似文献
110.
Abbi L. Engel Guan-Cheng Sun Ekram Gad Lauren R. Rastetter Katie Strobe Yi Yang Yushe Dang Mary L. Disis Hailing Lu 《Immunobiology》2013
Protein-bound polysaccharide-K (PSK) is a hot water extract from Trametes versicolor mushroom. It has been used traditionally in Asian countries for its immune stimulating and anti-cancer effects. We have recently found that PSK can activate Toll-like receptor 2 (TLR2). TLR2 is highly expressed on dendritic cells (DC), so the current study was undertaken to evaluate the effect of PSK on DC activation and the potential of using PSK as a vaccine adjuvant. In vitro experiments using mouse bone marrow-derived DC (BMDC) demonstrated that PSK induces DC maturation as shown by dose-dependent increase in the expression of CD80, CD86, MHCII, and CD40. PSK also induces the production of multiple inflammatory cytokines by DC, including IL-12, TNF-α, and IL-6, at both mRNA and protein levels. In vivo experiments using PSK as an adjuvant to OVAp323–339 vaccine showed that PSK as adjuvant leads to enlarged draining lymph nodes with higher number of activated DC. PSK also stimulates proliferation of OVA-specific T cells, and induces T cells that produce multiple cytokines, IFN-γ, IL-2, and TNF-α. Altogether, these results demonstrate the ability of PSK to activate DC in vitro and in vivo and the potential of using PSK as a novel vaccine adjuvant. 相似文献