全文获取类型
收费全文 | 82634篇 |
免费 | 5806篇 |
国内免费 | 3758篇 |
专业分类
耳鼻咽喉 | 353篇 |
儿科学 | 1482篇 |
妇产科学 | 859篇 |
基础医学 | 13061篇 |
口腔科学 | 1670篇 |
临床医学 | 6908篇 |
内科学 | 14411篇 |
皮肤病学 | 1032篇 |
神经病学 | 7735篇 |
特种医学 | 1316篇 |
外国民族医学 | 15篇 |
外科学 | 4852篇 |
综合类 | 13963篇 |
现状与发展 | 22篇 |
预防医学 | 4901篇 |
眼科学 | 969篇 |
药学 | 10579篇 |
10篇 | |
中国医学 | 2585篇 |
肿瘤学 | 5475篇 |
出版年
2024年 | 172篇 |
2023年 | 874篇 |
2022年 | 2217篇 |
2021年 | 3000篇 |
2020年 | 2414篇 |
2019年 | 2069篇 |
2018年 | 2042篇 |
2017年 | 2354篇 |
2016年 | 2681篇 |
2015年 | 3040篇 |
2014年 | 5083篇 |
2013年 | 5704篇 |
2012年 | 5386篇 |
2011年 | 6013篇 |
2010年 | 4762篇 |
2009年 | 4630篇 |
2008年 | 4760篇 |
2007年 | 4616篇 |
2006年 | 4148篇 |
2005年 | 3887篇 |
2004年 | 3182篇 |
2003年 | 2717篇 |
2002年 | 2073篇 |
2001年 | 1782篇 |
2000年 | 1540篇 |
1999年 | 1319篇 |
1998年 | 1228篇 |
1997年 | 1072篇 |
1996年 | 916篇 |
1995年 | 729篇 |
1994年 | 699篇 |
1993年 | 586篇 |
1992年 | 505篇 |
1991年 | 473篇 |
1990年 | 394篇 |
1989年 | 310篇 |
1988年 | 295篇 |
1987年 | 286篇 |
1986年 | 255篇 |
1985年 | 361篇 |
1984年 | 317篇 |
1983年 | 210篇 |
1982年 | 244篇 |
1981年 | 191篇 |
1980年 | 164篇 |
1979年 | 109篇 |
1978年 | 91篇 |
1977年 | 77篇 |
1976年 | 67篇 |
1975年 | 53篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
11.
《Vaccine》2019,37(24):3234-3240
Leucine aminopeptidase (FhLAP) and cathepsin L1 (FhCL1) of Fasciola hepatica play a critical role in parasite feeding, migration through host tissue, and immune evasion. These antigens have been tested for immune protection as single components with variable degrees of success. The chimeric-protein approach could improve protection levels against fasciolosis. Previously, we reported the design and construction of a chimeric protein composed of antigenic sequences of FhLAP and FhCL1 of F. hepatica. The goal of the present study was to express and evaluate the immune-protective capacity of this chimeric protein (rFhLAP-CL1) in sheep. Animals were randomly allocated into five groups with five animals in each group. Groups 1, 2 and 3 were immunized twice with 100 μg, 200 μg and 400 μg of rFhLAP-CL1 emulsified with Quil A adjuvant, whereas groups 4 and 5 were the adjuvant control and infection control groups, respectively. The animals were then challenged with 200 metacercariae two weeks after the rFhLAP-CL1 booster. The fluke burden was reduced by 25.5%, 30.7% (p < 0.05) and 46.5% (p < 0.01) in sheep immunized with 100 μg, 200 μg and 400 μg of chimeric protein, respectively, in comparison to the infection control group. There was a reduction of 22.7% (p < 0.05) and 24.4% (p < 0.01) in fecal egg count in groups 2 and 3, respectively, compared to the infection control group. Sheep immunized with chimeric protein produced F. hepatica excretion-secretion product-specific total IgG antibody, which were increased after challenge. Moreover, the levels of rFhLAP-CL1-specific IgG1 and IgG2 isotypes in immunized sheep increased rapidly two weeks after the first immunization and were significantly more elevated than those of the control groups, indicating a mixed Th1/Th2 response. This is a preliminary evaluation of the chimeric protein rFhLAP-CL1 as a possible immunogen against F. hepatica infection in sheep. 相似文献
12.
This study aimed to observe the therapeutic effects of magnesium lithospermate B on acute and chronic colitis induced by dextran sodiumsulfate (DSS) and the role of inflammasome complex (NOD-like receptor protein, NLRP; apoptosis-associated speck-like protein containing, ASC; caspase-1). Establishment of acute and chronic colitis models were by using 5% DSS oral administration in BALB/C male mice. Magnesium lithospermate B (240 mg/kg body weight) was given by subcutaneous injection. Samples were collected for biomarker assay, histological examination, immunohistochemical evaluation and western blot. There was obvious increase in TNF-α level and NLPR3, ASC, and caspase-1 expressions in acute and chronic colitis groups compared with the normal control. Significant decrease of the tumor necrosis factor-α level and the expressions of NLPR3, ASC, and caspase-1 were observed after treatment with magnesium lithospermate B. This study showed that magnesium lithospermate B could be used to treat acute and chronic colitis by inhibiting the activation of the NLRP3/ASC/Caspase-1 pathway. 相似文献
13.
目的 探讨γ干扰素诱导蛋白30(IFI 30)、程序性死亡因子配体1(PD-L1)在人脑胶质瘤中的表达及与病人预后的关系。方法 选择2015年5月~2019年5月手术切除的103例人脑胶质瘤组织和瘤旁组织,采用免疫组织化学染色检测IFI 30、PD-L1表达情况。随访24个月,记录无进展生存期和总生存期。结果 胶质瘤组织IFI 30、PD-L1高表达率[分别为70.87%(73/103)、68.93%(71/103)]明显高于瘤旁组织[分别为19.42%(20/103)、21.36%(22/103);P<0.001]。胶质瘤组织IFI 30表达水平与PD-L1表达水平呈明显正相关(r=0.583,P<0.05)。随访24个月,生存75例,死亡28例;多因素logistic回归分析显示,IFI 30高表达、PD-L1高表达是增加病人死亡风险的独立危险因素(P<0.05)。生存曲线分析显示,IFI 30高表达组2年累积生存率(64.52%)和2年累积无进展生存率(65.56%)均明显低于低表达组(分别为82.25%、89.45%;P<0.05)。PD-L1高表达组2年累积生存率(61.78%)和2年累积无进展生存率(60.14%)均明显低于低表达组(分别为88.52%、79.86%;P<0.05)。结论 人脑胶质瘤组织IFI 30、PD-L1呈高表达,与病人不良预后密切相关。 相似文献
14.
目的:总结富亮氨酸胶质瘤失活1蛋白(LGI1)抗体阳性边缘性脑炎的临床和影像特点及诊疗预后。
方法:报道我院1例LGI1抗体阳性相关边缘性脑炎并文献复习。结果:患者女性,60岁,表现为渐进性加重
的记忆力减退、癫痫发作(全身强直阵挛发作,面-臂肌张力障碍发作)、低钠血症和轻度精神行为异常。颅 脑MRI-T2/Flair序列提示双侧颞叶(左侧为甚)内侧、海马异常高信号。脑脊液抗LGI1抗体阳性(++)。经激
素治疗症状有所改善。检索既往报道LGI1抗体阳性边缘性脑炎患者237例,多数呈急性、亚急性起病,最
常见是记忆障碍、癫痫(含面-臂肌张力障碍发作)和低钠血症,头颅MRI(特别是MRI-T2/Flair序列)显示单
侧或者双侧海马区、颞叶异常多见,早期免疫治疗预后良好。结论:LGI1抗体阳性相关边缘性脑炎有其特
有的临床特点,免疫治疗可明显改善患者预后。 相似文献
15.
随着对肿瘤热疗和肿瘤免疫微环境(TIME)的深入研究,近年来热疗对TIME的作用越来越受到学者们的重视。本文就目前国内外研究进展,对热疗与TIME中几类主要免疫细胞和免疫相关细胞因子的影响及作用机制作一综述。全面而透彻的了解热疗对TIME的调控作用,有助于为肿瘤治疗提供新的思路和方法。 相似文献
16.
目的:观察灯盏乙素(Scu)对β淀粉样蛋白(Aβ)诱导的细胞模型中1,4,5-三磷酸肌醇受体(IP3R)-Ca2+途径的影响,探讨其在阿尔茨海默病(AD)病程中可能发挥的积极作用。方法:选用神经母细胞瘤细胞分为对照组、Scu处理组、Aβ处理组、Aβ+Scu (高、中、低)处理组及Aβ+IP3R拮抗剂组,用CCK-8法筛选药物浓度并检测各组细胞生存率;用酶联免疫吸附法检测各组细胞中1,4,5-三磷酸肌醇(IP3)的含量;用蛋白印迹和实时荧光定量聚合酶链反应方法检测各组细胞IP3R和凋亡相关因子Caspase-3、Bcl-2、Bax的蛋白及mRNA的表达水平;用激光共聚焦显微镜观察各组细胞内Ca2+浓度的变化;用AnnexinV/PI双染法测定各组细胞的凋亡率。结果:与对照组和Scu处理组相比,Aβ处理组细胞存活率下降,IP3含量升高,IP3R、Bax和Caspase-3的蛋白及mRNA表达上调,Bcl-2蛋白及mRNA的表达下调,细胞胞浆内Ca2+浓度及细胞凋亡率升高;Aβ+Scu处理组细胞中各检测指标的变化与Aβ处理组的结果正好相反,IP3R通道下游指标的变化与Aβ+IP3R拮抗剂组基本一致。结论:Scu能够下调通路蛋白IP3、IP3R的表达,抑制Aβ介导的Ca2+内流所致的细胞凋亡,可能通过对IP3R-Ca2+途径的调控来影响AD病程。 相似文献
17.
《Joint, bone, spine : revue du rhumatisme》2019,86(3):335-341
ObjectiveRetinol-binding protein 4 (RBP4), systemic inflammation and insulin resistance (IR) are linked, yet the determinants of RBP4 and its impact on IR in rheumatoid arthritis (RA) are incompletely understood. The aim of this study was to explore the prevalence of IR in RA and investigate whether the serum levels of RBP4 were associated with IR in patients with RA.MethodsIn this study, 403 individuals with newly diagnosed and untreated RA were consecutively recruited. We calculated the Disease Activity Score assessed using 28-joint counts for swelling and tenderness (DAS28). Levels of serum RBP4, interleukin-6 (IL-6) and tumor necrosis factor (TNF) α were tested. IR was defined as Homeostasis model assessment for insulin resistance (HOMA-IR) index greater than or equal 2.40.ResultsIn those 403 patients, 68 (16.9%) were male and the median age was 43 years (IQR: 36–52). There was an evidently positive correlation between increased serum levels of RBP4 and increasing severity of RA (DAS28) (r = 0.403, P < 0.001). Furthermore, a modest positive correlation between levels of serum RBP4 and HOMA-IR score (r = 0.251; P < 0.0001) was found. Eighty-five patients (21.1%) in patients with RA were defined as IR (HOMA-IR ≥ 2.40), which was significantly higher than in normal cases (4.7%). In the patients with IR, serum levels of RBP4 were higher when compared with those in patients free-IR P < 0.001. The IR distribution across the quartiles of RBP4 ranged between 5.0% (first quartile) to 39.0% (fourth quartile), P for trend < 0.001. For each 1unit increase of RBP4, the unadjusted and adjusted risk of IR increased by 8% (OR: 1.08; 95% CI: 1.05–1.11, P < 0.001) and 5% (1.05; 1.02–1.09, P = 0.001), respectively. When RBP4 was added to the model containing established significant risk factors, AUROC (standard error) was increased from 0.768 (0.025) to 0.807(0.021). A significant difference in the AUC between the established risk factors alone and the addition of RBP4 was observed (difference, 0.039[0.004]; P = 0.02).ConclusionElevated serum levels of RBP4 were associated with increased risk of IR and might be useful in identifying RA at risk for IR and/or impaired glucose tolerance for early prevention strategies, especially in obese and women patients 相似文献
18.
《Vaccine》2020,38(10):2315-2325
In the preparation of glycoconjugate vaccines in clinical practice, two highly immunogenic carrier proteins, CRM197 and tetanus toxoid (TT), are predominantly conjugated with the capsular polysaccharides (CPSs) of bacterial pathogens. In addition, TT has long been used as an effective vaccine to prevent tetanus. While these carrier proteins play an important role in immunogenicity and vaccine design alike, their defined human major histocompatibility complex class II (MHCII) T cell epitopes are inadequately characterized. In this current work, we use mass spectrometry to identify the peptides from these carrier proteins that are naturally processed and presented by human B cells via MHCII pathway. The MHCII-presented peptides are screened for their T cell stimulation using primary CD4+ T cells from four healthy adult donors. These combined methods reveal a subset of eleven CD4+ T cell epitopes that proliferate and stimulate human T cells with diverse MHCII allelic repertoire. Six of these peptides stand out as potential immunodominant epitopes by responding in three or more donors. Additionally, we provide evidence of these natural epitopes eliciting more significant T cell responses in donors than previously published TT peptides selected from T cell epitope screening. This study serves toward understanding carrier protein immune responses and thus enables the use of these peptides in developing novel knowledge-based vaccines to combat persisting problems in glycoconjugate vaccine design. 相似文献
19.
Brenda Laky Isabella Alram Julia K. Frank Leo Pauzenberger Werner Anderl Karl-Heinz Wagner Philipp R. Heuberer 《Journal of orthopaedic research》2020,38(9):2074-2082
Increasing numbers of arthroplasties are also accompanied by postoperative infections. The main purpose was to evaluate preoperative serum bilirubin levels between patients with and without infections after shoulder and knee arthroplasties. For this retrospective case-control single-center study, a total of 108 patients were extracted from a prospectively collected database. Eighteen patients with infections after shoulder (n = 8) and knee (n = 10) arthroplasty were matched by age, gender, and implant type in a 1:5-scenario to 90 patients (40 shoulders and 50 knees) without postoperative infection. Demographic data, preoperative blood parameters, and postoperative infection-related outcomes were evaluated. Total bilirubin was the only preoperative parameter significantly different between the infection (8.21 ± 3.25 μmol/L or 0.48 ± 0.19 mg/dL) and noninfection (10.78 ± 4.62 μmol/L or 0.63 ± 0.27 mg/dL; P = .014) group, while C-reactive protein and other liver parameters were similar between the groups. Significantly more controls (92.1%) had preoperative bilirubin levels above 8.72 μmol/L or 0.51 mg/dL than cases (7.9%; P = .007). The 5-year infection survival-rate was 65.6% for patients with preoperative bilirubin levels < 8.72 μmol/L or < 0.51 mg/dL and 91.2% with ≥ 8.72 μmol/L or ≥ 0.51 mg/dL. Mildly decreased preoperative bilirubin levels with a cutoff at 8.72 μmol/L or 0.51 mg/dL were significantly associated to patients with infections after shoulder and knee arthroplasty. There were no differences in other blood parameters or comorbidities between patients with infections and their matched-controls. 相似文献
20.
《Nutrition, metabolism, and cardiovascular diseases : NMCD》2022,32(12):2883-2889
Background and aimsCoronary artery disease (CAD) is the principal cause of death in individuals with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to use genetic epidemiology to study the association between de novo lipogenesis (DNL), one of the major pathways leading to NAFLD, and CAD risk.Methods and resultsDNL susceptibility genes were used as instruments and selected using three approaches: 1) genes that are associated with both high serum triglycerides and low sex hormone-binding globulin, both downstream consequences of DNL (unbiased approach), 2) genes that have a known role in DNL (biased approach), and 3) genes that have been associated with serum fatty acids, used as a proxy of DNL. Gene-CAD effect estimates were retrieved from the meta-analysis of CARDIoGRAM and the UK Biobank (~76014 cases and ~264785 controls). Effect estimates were clustered using a fixed-effects meta-analysis. Twenty-two DNL susceptibility genes were identified by the unbiased approach, nine genes by the biased approach and seven genes were associated with plasma fatty acids. Clustering of genes selected in the unbiased and biased approach showed a statistically significant association with CAD (OR:1.016, 95%CI:1.012; 1.020 and OR:1.013, 95%CI:1.007; 1.020, respectively), while clustering of fatty acid genes did not (OR:1.004, 95%CI:0.996–1.011). Subsequent exclusion of potential influential outliers did reveal a statistically significant association (OR:1.009, 95%CI:1.000; 1.018).ConclusionsDNL susceptibility genes are associated with an increased risk of CAD. These findings suggest that DNL may be involved in the pathogenesis of CAD and favor further development of strategies that target NAFLD through DNL. 相似文献