全文获取类型
收费全文 | 15736篇 |
免费 | 752篇 |
国内免费 | 409篇 |
专业分类
耳鼻咽喉 | 35篇 |
儿科学 | 144篇 |
妇产科学 | 296篇 |
基础医学 | 1950篇 |
口腔科学 | 242篇 |
临床医学 | 1044篇 |
内科学 | 2080篇 |
皮肤病学 | 211篇 |
神经病学 | 854篇 |
特种医学 | 266篇 |
外国民族医学 | 6篇 |
外科学 | 770篇 |
综合类 | 2385篇 |
现状与发展 | 1篇 |
预防医学 | 771篇 |
眼科学 | 225篇 |
药学 | 3517篇 |
6篇 | |
中国医学 | 1325篇 |
肿瘤学 | 769篇 |
出版年
2024年 | 9篇 |
2023年 | 207篇 |
2022年 | 326篇 |
2021年 | 570篇 |
2020年 | 652篇 |
2019年 | 453篇 |
2018年 | 389篇 |
2017年 | 628篇 |
2016年 | 640篇 |
2015年 | 576篇 |
2014年 | 1385篇 |
2013年 | 2122篇 |
2012年 | 1775篇 |
2011年 | 1571篇 |
2010年 | 1152篇 |
2009年 | 945篇 |
2008年 | 796篇 |
2007年 | 406篇 |
2006年 | 365篇 |
2005年 | 335篇 |
2004年 | 267篇 |
2003年 | 182篇 |
2002年 | 133篇 |
2001年 | 56篇 |
2000年 | 41篇 |
1999年 | 27篇 |
1998年 | 46篇 |
1997年 | 40篇 |
1996年 | 36篇 |
1995年 | 28篇 |
1994年 | 15篇 |
1993年 | 14篇 |
1992年 | 9篇 |
1990年 | 17篇 |
1989年 | 11篇 |
1988年 | 15篇 |
1987年 | 13篇 |
1985年 | 64篇 |
1984年 | 77篇 |
1983年 | 87篇 |
1982年 | 85篇 |
1981年 | 55篇 |
1980年 | 58篇 |
1979年 | 42篇 |
1978年 | 36篇 |
1977年 | 28篇 |
1976年 | 23篇 |
1975年 | 24篇 |
1974年 | 20篇 |
1973年 | 24篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
《Vaccine》2022,40(11):1594-1605
In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes. 相似文献
2.
Ahmed M. Abu El-Asrar Ajmal Ahmad Eef Allegaert Mohammad Mairaj Siddiquei Priscilla W. Gikandi Gert De Hertogh 《Ocular immunology and inflammation》2020,28(4):575-588
ABSTRACT
Purpose
To investigate the expression of IL-11 and its receptor IL-11Rα and to quantify density of CD163+ M2 macrophages in proliferative diabetic retinopathy (PDR). 相似文献3.
《Vaccine》2019,37(31):4382-4391
Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8+ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα+ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice. 相似文献
4.
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
5.
Ewelina Kazimierczyk Andrzej Eljaszewicz Paula Zembko Ewa Tarasiuk Malgorzata Rusak Agnieszka Kulczynska-Przybik Marta Lukaszewicz-Zajac Karol Kaminski Barbara Mroczko Maciej Szmitkowski Milena Dabrowska Bozena Sobkowicz Marcin Moniuszko Agnieszka Tycinska 《Pharmacological reports : PR》2019,71(1):73-81
Background
Acute myocardial infarction (AMI) causes irreversible myocardial damage and release of inflammatory mediators, including cytokines, chemokines and miRNAs. We aimed to investigate changes in the levels of cytokines (IL-6, TNF-α and IL-10), miRNAs profiles (miR-146 and miR-155) and distribution of different monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) in the acute and post-healing phases of AMI.Methods
In eighteen consecutive AMI patients (mean age 56.78?±?12.4 years, mean left ventricle ejection fraction – LVEF: 41.9?±?9.8%), treated invasively, monocyte subsets frequencies were evaluated (flow cytometry), cytokine concentrations were analyzed (ELISA) as well as plasma miRNAs were isolated twice – on admission and after 19.2?±?5.9 weeks of follow-up. Measurements were also performed among healthy volunteers.Results
AMI patients presented significantly decreased frequencies of classical cells in comparison to healthy controls (median 71.22% [IQR: 64.4–79.04] vs. 84.35% [IQR: 81.2–86.7], p?=?0.001) and higher percent of both intermediate and non-classical cells, yet without statistical significance (median 6.54% [IQR: 5.14–16.64] vs. 5.87% [IQR: 4.48–8.6], p?=?0.37 and median 5.99% [IQR: 3.39–11.5] vs. 5.26% [IQR: 3.62–6.2], p?=?0.42, respectively). In AMI patients both, analyzed plasma miRNA concentrations were higher than in healthy subjects (miR-146: median 5.48 [IQR: 2.4–11.27] vs. 1.84 [IQR: 0.87–2.53], p?=?0.003; miR-155: median 25.35 [IQR: 8.17–43.15] vs. 8.4 [IQR: 0.08–16.9], p?=?0.027, respectively), and returned back to the values found in the control group in follow-up. miR-155/miR-146 ratio correlated with the frequencies of classical monocytes (r=0.6, p?=?0.01) and miR-155 correlated positively with the concentration of inflammatory cytokines ? IL-6 and TNF-α.Conclusions
These results may suggest cooperation of both pro-inflammatory and anti-inflammatory signals in AMI in order to promote appropriate healing of the infarcted myocardium. 相似文献6.
Inflammation plays a critical role in the development of ventilator-induced lung injury (VILI). Endoplasmic reticulum (ER) stress is associated with a variety of diseases through the modulation of inflammatory responses. However, little is known about how ER stress is implicated in VILI. In this study, murine mechanical ventilation models were constructed. Total protein and inflammatory cytokines were measured in bronchoalveolar lavage fluid (BALF), and lung tissue injury was assessed by histology. Our data revealed that mice subjected to high tidal ventilation (TV) for 4 h showed more severe pulmonary edema and inflammation than those of mice with spontaneous breathing and low TV-treatment. In addition, the high TV-treated animals upregulated the ER stress markers GRP78, CHOP, p-IRE1α, TRAF2, and p-NF-κB expression at both the mRNA and protein levels in lung tissue. Administration of thapsigargin exacerbated the histological changes, inflammation and expression of GRP78 and CHOP after high TV, but treatment with ER stress and IRE1α kinase inhibitors attenuated the pathological damage and downregulated the high expression of GRP78, CHOP, p-IRE1α, TRAF2, and p-NF-κB, suggesting that ER stress is involved in VILI though the IRE1α/TRAF2/NF-κB signaling pathway in mice. 相似文献
7.
报道新化合物A-失碳-17β-羟基-17α-乙炔基-Δ3(5),9(10)-雌甾二烯-2-酮2的合成。文中探讨了用炔钾粗品对A-失碳-Δ3(5),9(10)-雌甾二烯-2,17-二酮1和A-失碳-6β,19-环氧-Δ3-雄甾-2,17-二酮3的选择性炔化,分别得标题化合物2(44%)及A-失碳-17β-羟基-17α-乙炔基-6β,19-环氧-Δ3雄甾-2-酮4(65%),4经还原性破开环氧、去羟甲基和去醋酰氧基合成了标题化合物2。四步总收率为34%。 相似文献
8.
9.
体外短波热疗联合前列腺灸及哈乐治疗非细菌性前列腺炎和前列腺痛疗效观察 总被引:5,自引:1,他引:4
目的 探讨慢性非细菌性前列腺炎(CNP)和前列腺痛(PD)的治疗方法。方法 应用体外短波热疗联合前列腺灸及α1A-肾上腺素能受体阻滞剂哈乐治疗CNP和PD患者26例,疗程8周。观察治疗前后前列腺炎症状评分(CPSI)与最大尿流率(MFR)变化。结果 有效率为80.8%。治疗前后CPSI和MFR均有显著改善(P〈0.05)。结论 体外短波热疗联合前列腺灸及哈乐治疗CNP和PD安全有效。 相似文献
10.
血清α—L-岩藻糖苷酶(AFU)对原发性肝癌(PHC)的诊断意义 总被引:1,自引:0,他引:1
目的研究血清α-L-岩藻糖苷酶(AFU)对原发性肝癌的诊断意义。方法分别测定20例正常对照者、45例慢性乙型肝炎、40例肝硬化、50例转移性肝癌及35例原发性肝癌患者的血清AFU。结果原发性肝癌组的血清AFU浓度和阳性率显著高手其他各组。结论血清AFU对原发性肝癌的诊断有重要价值。 相似文献