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排序方式: 共有5012条查询结果,搜索用时 15 毫秒
1.
目的 探索Gadd45β和Gadd45γ在亚砷酸钠所致的MIHA细胞周期改变中的作用,为砷中毒的人群防治提供依据。方法 收集贵州省兴仁县雨樟镇交乐病区砷中毒人群以及格沙屯正常人群分别作为砷中毒组和对照组,实时荧光定量PCR检测各组人群Gadd45β和Gadd45γ基因mRNA表达水平。同时,分别以不同剂量亚砷酸钠、不同时间处理MIHA细胞,流式细胞术测定细胞周期改变情况,实时荧光定量PCR和免疫印迹法分别检测Gadd45β和Gadd45γ基因mRNA表达水平和蛋白表达情况。在上述实验基础上,针对Gadd45β和Gadd45γ基因分别设计的siRNA作用于染砷的MIHA细胞,反向验证Gadd45β和Gadd45γ基因在砷致细胞周期改变过程中的影响。统计学分析采用独立样本t检验比较两组间差异,采用单因素方差比较多组间差异。结果 人群实验研究发现,与对照组相比,砷中毒患者Gadd45β和Gadd45γ基因mRNA表达水平升高(t = 2.576,P = 0.011;t = 2.312,P = 0.022);MIHA细胞中,随亚砷酸钠染毒剂量、染毒时间增加,细胞G2/M期比例明显升高(F剂量 = 340.136,P<0.001;F时间 = 49.194,P<0.001);在相对较低亚砷酸钠浓度(低于20 μmol/L)、一定时间内(低于48 h)Gadd45β和Gadd45γ基因mRNA和蛋白表达水平随染砷剂量、染砷时间升高而升高,超过该浓度范围和作用时间后,出现表达下降的现象(Gadd45β:F剂量-蛋白 = 37.568,P<0.001;F剂量- mRNA = 9.771,P<0.001;F时间-蛋白 = 61.144,P<0.001;F时间- mRNA = 46.366,P = 0.001;Gadd45γ:F剂量-蛋白 = 12.989,P = 0.001;F剂量- mRNA = 23.613,P<0.001;F时间-蛋白 = 27.425,P<0.001;F时间- mRNA = 37.969,P<0.001)。转染siRNA分别下调Gadd45β和Gadd45γ的表达后,细胞周期都出现G2/M期比例下调(t = 3.053,P = 0.038;t = 14.47,P<0.001)。结论 砷致Gadd45β和Gadd45γ基因表达水平升高在其诱导MIHA细胞出现G2/M期阻滞过程中发挥重要作用。  相似文献   
2.
目的探讨血清丁酰胆碱酯酶(BuChE)、干扰素-γ(IFN-γ)、同型半胱氨酸(Hcy)水平与血管性痴呆(VD)的关系及艾地苯醌干预作用。方法回顾性选取2016年8月至2019年8月沈阳市第七人民医院收治的VD患者94例为病例组,同期94例健康体检者为对照组。对比2组入院或体检当日血清BuChE、IFN-γ、Hcy水平,病例组不同病情程度患者血清BuChE、IFN-γ、Hcy水平,以Spearman相关系数分析探讨血清BuChE、IFN-γ、Hcy水平与病情程度的相关性。并将病例组以随机数字表法分为A组、B组,各47例。常规治疗基础上,A组采取尼莫地平治疗,B组采取艾地苯醌治疗,均治疗3个月。比较A组、B组治疗前、治疗3个月后血清BuChE、IFN-γ、Hcy水平、认知功能评分(MMSE),统计治疗效果。结果病例组血清BuChE、IFN-γ、Hcy水平为(7431.09±823.31)U/L、(193.12±11.68)pg/mL、(36.65±4.47)μmol/L均明显高于对照组[(5276.52±765.84)U/L、(128.26±8.47)pg/mL、(7.93±2.21)μmol/L],差异有统计学意义(P<0.05);随患者病情程度加重其血清BuChE、IFN-γ、Hcy水平呈升高趋势(P<0.05);血清BuChE、IFN-γ、Hcy水平与血管性痴呆患者病情程度呈正相关(r=0.427、0.684、0.572,P<0.05)。A、B组治疗3个月后血清BuChE、IFN-γ、Hcy水平均较治疗前降低,且B组低于A组[(5681.39±594.25)vs.(6194.27±685.03)U/L,(136.24±8.46)vs.(153.18±9.8)pg/mL,(20.24±3.57)vs.(24.36±4.09)μmol/L],差异有统计学意义(P<0.05);2组治疗3个月后MMSE评分均较治疗前提高,且B组高于A组[(23.98±2.73)vs.(20.26±3.08)分],差异有统计学意义(P<0.05);B组总有效率高于A组(93.62%vs.76.60%),差异有统计学意义(P<0.05)。结论VD患者存在血清BuChE、IFN-γ、Hcy异常表达情况,且与病情进展关系密切,艾地苯醌能通过降低上述血清因子水平改善患者认知功能,效果显著。  相似文献   
3.
Vγ9Vδ2 T cells are attractive effector cells for immunotherapy with potent cytotoxic activity against a variety of malignant cells. However, the effect of Vγ9Vδ2 T cells on chemotherapy-resistant acute myeloid leukemia (AML) blasts, especially highly refractory leukemia stem cells (LSCs) is still unknown. In this study, we investigated the effect of cytotoxicity of allogeneic Vγ9Vδ2 T cells on chemotherapy-resistant AML cell lines, as well as on primary AML blasts and LSCs obtained from refractory AML patients. The results indicated that Vγ9Vδ2 T cells can efficiently kill drug-resistant AML cell lines in vitro and in vivo, and the sensitivity of AML cells to Vγ9Vδ2 T cell–mediated cytotoxicity is not influenced by the sensitivity of AML cells to chemotherapy. We further found that Vγ9Vδ2 T cells exhibited a comparable effect of cytotoxicity against LSCs to primary AML blasts. More importantly, we revealed that the CD226–extracellular signal–regulatory kinase1/2 (ERK1/2)–lysosome-associated membrane protein 1 (LAMP1) pathway is an important mechanism for Vγ9Vδ2 T cell–induced cytotoxicity against AML cells. First, Vγ9Vδ2 T cells recognized AML cells by receptor-ligand interaction of CD226–Nectin-2, which then induced ERK1/2 phosphorylation in Vγ9Vδ2 T cells. Finally, triggering the movement of lytic granules toward AML cells induced cytolysis of AML cells. The expression level of Nectin-2 may be used as a novel marker to predict the susceptibility/resistance of AML cells to Vγ9Vδ2 T cell treatment.  相似文献   
4.
目的 探讨巨细胞病毒(CMV)肝炎患儿血清干扰素-γ(IFN-γ)和白细胞介素-18(IL-18)水平变化及其与预后的关系。方法 2017年1月~2019年6月我院收治的95例CMV肝炎患儿(轻症66例,重症29例)和90例健康儿童,给予CMV肝炎儿童更昔洛韦治疗6 w,采用ELISA法检测血清IFN-γ和IL-18水平。应用受试者工作特征曲线下面积(AUROC)分析血清细胞因子预测CMV肝炎患儿的转归。结果 轻症CMV肝炎患儿血清IFN-γ、IL-18、ALT和TBIL水平分别为(7.7±2.9)mmol/L、(56.9±5.7)pg/L、(69.8±11.3)U/L和(75.4±16.7)μmol/L,重症CMV肝炎患儿分别为(16.6±4.1)mmol/L、(89.5±8.3)pg/L、(104.7±13.2)U/L和(235.7±20.4)μmol/L,均显著高于健康儿童【分别为(2.1±1.1)mmol/L、(33.7±4.9)pg/L、(19.6±3.1)U/L和(8.3±2.7)μmol/L, P<0.05】;在治疗后,轻症CMV肝炎患儿血清IFN-γ、IL-18、ALT和TBIL水平分别为(2.2±0.9)mmol/L、(34.1±5.4)pg/L、(21.2±4.3)U/L和(13.4±4.1)μmol/L,显著低于重症CMV肝炎患儿【(4.1±0.6)mmol/L、(40.6±7.9)pg/L、(46.5±7.5)U/L和(26.5±3.4)μmol/L,P<0.05】;在95例患儿中,痊愈80例,未恢复15例;有效患儿血清IFN-γ、IL-18、ALT和TBIL水平显著低于无效患儿,差异有统计学意义(均P<0.05);以血清IFN-γ预测CMV肝炎不良转归(无效)的敏感度为86.7%,特异性为96.3%,血清IL-18预测的敏感度为93.3%,特异性为73.8%。结论 CMV肝炎患儿血清IFN-γ和IL-18水平明显升高,在治疗后其血清水平下降缓慢者,可能预后不良,值得进一步监测。  相似文献   
5.
Psychosis is a common and intractable disorder of hospitalization, especially in patients hospitalized in Intensive Care Unit (ICU). Along with the widely use of multiple antibiotics in community-acquired infection and hospital-acquired infection, the occurrence of antibiotic-associated neurological disorders has become more frequently. However, antibiotic neurotoxicity is often overlooked or misinterpreted. In this review, we summarized the neurological disorders caused by antibacterial agent usage and firstly systematically formulated the pathogenesis of antibiotic-associated neurotoxic reactions. Precautions of the complications are critical in preventing serious clinical outcome as the inducement is curable. Regular neurological physical examination, electroencephalogram (EEG) examination, lumbar puncture and therapeutic drug monitoring closely are essential for early diagnosis and differential diagnosis.  相似文献   
6.
目的验证蛋白酶体抑制剂硼替佐米(Bortezomib,BTZ)对调节肺动脉平滑肌细胞瞬时受体通道蛋白表达的影响,探讨其对调节瞬时受体通道蛋白表达的分子机制。方法原代培养大鼠肺动脉平滑肌细胞,将细胞分为常氧组、常氧+BTZ组、低氧组及低氧+BTZ组,60 h后,通过免疫印迹法测定PPARγ、TRPC1、6蛋白的表达。另将原代培养的肺动脉平滑肌细胞分为低氧组、低氧+BTZ组、低氧+BTZ+T0070907组,60 h后,通过免疫印迹法测定TRPC1、6蛋白的表达。结果(1)与常氧组相比,低氧组、低氧+BTZ组细胞TRPC1蛋白的相对表达量分别为(158±11)%和(112±8)%,低氧+BTZ组细胞TRPC1蛋白表达量相较于低氧组明显降低(P<0.05);(2)与常氧组相比,低氧组、低氧+BTZ组细胞TRPC6蛋白的相对表达量分别为(146±9)%和(107±6)%,低氧+BTZ组细胞TRPC6蛋白表达量相较于低氧组明显降低(P<0.05);(3)与常氧组相比,低氧组、低氧+BTZ组细胞PPARγ蛋白的相对表达量分别为(65±7)%和(98±6)%,低氧+BTZ组细胞PPARγ蛋白表达量相较于低氧组明显升高(P<0.05);(4)与低氧组相比,低氧+BTZ组、低氧+BTZ+T0070907组,TRPC1蛋白的相关表达量分别为(65±7)%和(92±9)%,低氧+BTZ+T0070907组细胞TRPC1蛋白表达量相较于低氧+BTZ组明显升高(P<0.05);(5)与低氧组相比,低氧+BTZ组、低氧+BTZ+T0070907组TRPC6蛋白的相关表达量分别为(71±5)%和(97±7)%,低氧+BTZ+T0070907组细胞TRPC6蛋白表达量相较于低氧+BTZ组明显升高(P<0.05)。结论硼替佐米通过抑制低氧诱导的肺动脉平滑肌细胞PPARγ的下调,调节TRPC蛋白的表达。  相似文献   
7.
BackgroundMendelian susceptibility to mycobacterial disease (MSMD) is characterized by a selective predisposition to infections caused by intracellular pathogens, such as mycobacteria, due to impaired IFN-γ immunity. To date, 18 different genes associated with MSMD have been reported.ObjectivesThis review describes recent discoveries, a 2020–2021 update, in MSMD through the introduction of three novel genetic disorders, namely, AR IFN-γ, T-bet, and ZNFX1 complete deficiency, as well as molecular mechanisms underlying multifocal osteomyelitis in patients with this condition.SourcesPubMed databases were searched for reports of MSMD since January 2020. Relevant articles and their references were screened.ContentThe review covers a general overview, known genes, classifications, symptoms, and treatments for MSMD. MSMD is classified into two groups: isolated MSMD and syndromic MSMD. Among the 18 genes responsible, 13 cause isolated MSMD, which is characterized by selective predisposition to one or more mycobacterial and related infections, and 8 cause syndromic MSMD, which involves the combination of the mycobacterial disease infectious phenotype with additional clinical phenotypes. Among the three genetic etiologies described herein, AR IFN-γ deficiency is classified as isolated MSMD, whereas AR T-bet and ZNFX1 deficiency are classified as syndromic MSMD. Multifocal osteomyelitis is a representative symptom of MSMD, and a high frequency of multifocal osteomyelitis is reported in MSMD patients due to impaired IFN-γ responses, such as with AD IFN-γR1, AD IFN-γR2, or AD STAT1 deficiency. Impaired inhibition of osteoclast differentiation and bone resorption owing to a poor response to IFN-γ has been shown to be in association with multifocal osteomyelitis in MSMD.ImplicationsOver the past decade, genetic dissection by next-generation sequencing techniques has contributed to the understanding of the molecular bases of human immunity to mycobacteria. However, genetic etiologies are lacking for half of MSMD cases. Further studies will be needed to elucidate the pathogenesis of MSMD.  相似文献   
8.
目的探讨恩替卡韦分散片(ETV)治疗对高病毒载量慢性乙肝患者的T细胞亚群及血清脂联素(ADP)、干扰素-γ(IFN-γ)、白细胞介素-2(IL-2)水平的影响。方法从本院于2018年6月至2020年6月收治慢性乙肝患者中筛选经荧光定量PCR法测定HBV-DNA>2×105 IU/mL为高病毒载量86例进行研究,按随机数字表法分对照组和观察组,予以对照组常规减黄、保肝及营养支持等对症治疗,观察组在对症治疗基础上予以ETV治疗,均持续治疗6个月,比较两组T细胞亚群、病毒载量指标及Th1/Th2型与相关炎性因子水平。结果经治疗,两组CD3+、CD4+水平均见提升,CD8+水平有一定下降,观察组CD3+、CD4+水平较对照组更高,CD8+水平则更低(P<0.05);两组HBsAg、HBeAg及HBV-DNA载量水平均见相应降低,观察组低于对照组(P<0.05);两组ADP水平呈上升趋势,IFN-γ及IL-2水平均呈下降趋势,观察组ADP水平高于对照组,IFN-γ及IL-2水平均更低(P<0.05)。结论高病毒载量慢性乙肝患者应用恩替卡韦分散片治疗,有助于T细胞亚群改善,且较大程度降低了病毒载量水平,并增强了机体免疫功能。  相似文献   
9.
BackgroundCytokines and chemokines play critical roles in the pathogenesis of asthma. Azithromycin, a macrolides, is frequently used in asthmatic children with lower respiratory tract infection and is reported having anti-inflammatory and immunomodulatory effects. However, the effects of azithromycin on the expression of TNF-α, Th1- and Th2-related chemokines, and neutrophil chemoattractant are unknown. We investigated the in vitro effects of azithromycin on the expression of TNF-α, Th1-related chemokine interferon-γ-inducible protein-10 (IP-10/CXCL10), Th2-related chemokine macrophage-derived chemokine (MDC/CCL22) and neutrophil chemoattractant growth-related oncogene-α (GRO-α/CXCL1) in THP-1 cells as a model for human monocytes.MethodsTHP-1 cells were pretreated with various concentrations of azithromycin before Toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS) stimulation. TNF-α, IP-10, MDC and GRO-α were measured by ELISA. Intracellular signaling was investigated by pathway inhibitors and Western blot.ResultAzithromycin suppressed MDC and IP-10 expression in LPS-stimulated THP-1 cells. However, azithromycin had no effect LPS-induced TNF-α and GRO-α expression. Western blotting revealed that azithromycin suppressed LPS-induced phosphorylation of mitogen-activated protein kinase (MAPK)–JNK and ERK expression, and also suppressed LPS-induced phosphorylation of nuclear factor (NF) κB–p65 expression.ConclusionAzithromycin suppressed LPS-induced MDC expression via the MAPK–JNK and the NFκB–p65 pathway. Azithromycin also suppressed LPS-induced IP-10 via the MAPK–JNK/ERK and the NFκB–p65 pathway. Azithromycin may benefit asthmatic patients by suppressing chemokines expression.  相似文献   
10.
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