全文获取类型
收费全文 | 1303篇 |
免费 | 74篇 |
国内免费 | 27篇 |
专业分类
耳鼻咽喉 | 1篇 |
妇产科学 | 6篇 |
基础医学 | 215篇 |
口腔科学 | 50篇 |
临床医学 | 89篇 |
内科学 | 41篇 |
皮肤病学 | 3篇 |
神经病学 | 15篇 |
特种医学 | 28篇 |
外科学 | 84篇 |
综合类 | 71篇 |
预防医学 | 71篇 |
眼科学 | 7篇 |
药学 | 657篇 |
中国医学 | 10篇 |
肿瘤学 | 56篇 |
出版年
2023年 | 28篇 |
2022年 | 38篇 |
2021年 | 49篇 |
2020年 | 35篇 |
2019年 | 33篇 |
2018年 | 58篇 |
2017年 | 37篇 |
2016年 | 57篇 |
2015年 | 72篇 |
2014年 | 124篇 |
2013年 | 215篇 |
2012年 | 89篇 |
2011年 | 109篇 |
2010年 | 62篇 |
2009年 | 93篇 |
2008年 | 87篇 |
2007年 | 56篇 |
2006年 | 43篇 |
2005年 | 26篇 |
2004年 | 33篇 |
2003年 | 8篇 |
2002年 | 12篇 |
2001年 | 14篇 |
2000年 | 13篇 |
1999年 | 2篇 |
1998年 | 4篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1993年 | 2篇 |
排序方式: 共有1404条查询结果,搜索用时 15 毫秒
1.
Purnima Gogoi Geetika Kaur Nikhlesh K Singh 《World journal of gastroenterology : WJG》2022,28(46):6497-6511
Colorectal cancer (CRC) is the third most diagnosed cancer and the second leading cause of cancer-related mortality in the United States. Across the globe, people in the age group older than 50 are at a higher risk of CRC. Genetic and environmental risk factors play a significant role in the development of CRC. If detected early, CRC is preventable and treatable. Currently, available screening methods and therapies for CRC treatment reduce the incidence rate among the population, but the micrometastasis of cancer may lead to recurrence. Therefore, the challenge is to develop an alternative therapy to overcome this complication. Nanotechnology plays a vital role in cancer treatment and offers targeted chemotherapies directly and selectively to cancer cells, with enhanced therapeutic efficacy. Additionally, nanotechnology elevates the chances of patient survival in comparison to traditional chemotherapies. The potential of nanoparticles includes that they may be used simultaneously for diagnosis and treatment. These exciting properties of nanoparticles have enticed researchers worldwide to unveil their use in early CRC detection and as effective treatment. This review discusses contemporary methods of CRC screening and therapies for CRC treatment, while the primary focus is on the theranostic approach of nanotechnology in CRC treatment and its prospects. In addition, this review aims to provide knowledge on the advancement of nanotechnology in CRC and as a starting point for researchers to think about new therapeutic approaches using nanotechnology. 相似文献
2.
《Dental materials》2022,38(2):397-408
ObjectivesComposite restorations with calcium fluoride nanoparticles (nCaF2) can remineralize tooth structure through F and Ca ion release. However, the persistence of ion release is limited. The objectives for this study were to achieve long-term remineralization by developing a rechargeable nCaF2 nanocomposite and investigating the F and Ca recharge and re-release capabilities.MethodsThree nCaF2 nanocomposites were formulated: (1) BT-nCaF2:Bisphenol A glycidyl dimethacrylate (BisGMA) and triethylene glycol dimethacrylate (TEGDMA); (2) PE-nCaF2:Pyromellitic glycerol dimethacrylate (PMGDM) and ethoxylated bisphenol A dimethacrylate (EBPADMA); (3) BTM-nCaF2:BisGMA, TEGDMA, and Bis[2-(methacryloyloxy)ethyl] phosphate (Bis-MEP). All formulations contained 15% nCaF2 and 55% glass particles. Initial flexural strength and elastic modulus, F and Ca ion release, recharge and re-release were tested and compared to three commercial fluoride-containing materials.ResultsBT and BTM nCaF2 composites were 3–4 times stronger and had elastic modulus 2 times that of resin-modified glass ionomer controls. PE-nCaF2 had comparable strength to RMGIs. All nCaF2 composites had significant F and Ca ion release and ion rechargeability. In F and Ca recharging cycles, PE-nCaF2 had the highest ion recharging capability among nCaF2 groups, followed by BT-nCaF2 and BTM-nCaF2 (p < 0.05). For all recharge cycles, ion release maintained similar levels, demonstrating long-term ion release was possible. Furthermore, after the final recharge cycle, nCaF2 nanocomposites provided continuous ion release for 42 days without further recharge.SignificanceNovel nCaF2 rechargeable nanocomposites exhibited significant F and Ca ion release over multiple recharge cycles, demonstrating continuous long-term ion release. These nanocomposites are promising restorations with lasting remineralization potential. 相似文献
3.
《Clinical breast cancer》2022,22(6):507-514
Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC. 相似文献
4.
《Dental materials》2022,38(3):517-528
ObjectivePrevious studies have shown that particles can be released from dental titanium (Ti)- and zirconia (ZrO2)-implants. Titanium dioxide (TiO2)- and ZrO2-particles were compared regarding their toxicity and intranuclear cell uptake as well as the adhesion of various anaerobic bacteria on Ti- and ZrO2-implants.MethodsCyto- and genotoxicity of TiO2-microparticles (TiO2-MPs) and TiO2-nanoparticles (TiO2-NPs) in periodontal ligament (PDL)-hTERT cells were determined with XTT test and DNA damage with comet assay. Particle sizes of TiO2- and ZrO2-particles were measured with scanning electron microscope. Intranuclear uptake in PDL-hTERT cells was determined with laser scanning confocal microscopy. Adhesions of relevant anaerobic mouth bacteria Porphyromonas gingivalis, Prevotella intermedia and Aggregatibacter actinomycetemcomitans on Ti- and ZrO2-implants were investigated by cultivation and counting bacterial colonies.ResultsParticle size measurements revealed that 99% of the TiO2-NPs had a size below 100 nm and 88% of the TiO2-MPs sizes were between 50 and 200 nm. Following EC50 values were found for particles (mg/l): 92 (TiO2-MPs) and 15 (TiO2-NPs). A significant increase in olive tail moment (OTM) was found for TiO2-NPs at a concentration of 1/10 EC50. TiO2- and ZrO2-NPs had a higher intranuclear cell uptake efficiency, compared to corresponding TiO2- and ZrO2-MPs. All investigated particles could be detected in cell nucleus. Adhesion of all investigated bacterial species was significantly higher on Ti-implants, compared to ZrO2-implants.ConclusionTi usually develops an oxide layer (TiO2). Particles released from Ti-implants should be TiO2-particles or Ti-particles coated with a TiO2-layer. Toxicity of released Ti-particles depends on their oxidation state and on their size (NP or MP). Particularly, NPs were more cyto- and genotoxic compared to the corresponding MPs. TiO2- and ZrO2-NPs showed a significant increase in the intranuclear cell uptake ratio at higher exposure concentration, compared to lower concentrations and consequently might lead to a higher potential of DNA damage. Adhesion of bacteria to ZrO2-implants is reduced, compared to Ti-implants. Therefore, ZrO2-implants might contribute to reduced biological complications (e.g. periimplantitis). 相似文献
5.
摘要:抗生素的研发与使用有效杀灭和抑制了众多病原菌,挽救了无数人的生命,但由于抗生素的不合理使用,导致细菌耐
药不断出现,耐药菌的感染已严重地威胁人类的生命健康。为此,本文主要对近年来临床上常用的抗生素如β-内酰胺类、喹诺酮
类、氨基糖苷类药物以及新型抗菌药物如抗菌肽和纳米颗粒的应用研究进行总结分析与探讨,为临床上治疗疾病提供一些参考。 相似文献
6.
《Saudi Pharmaceutical Journal》2022,30(6):655-668
Most vaccines approved by regulatory bodies are administered via intramuscular or subcutaneous injections and have shortcomings, such as the risk of needle-associated blood infections, pain and swelling at the injection site. Orally administered vaccines are of interest, as they elicit both systemic and mucosal immunities, in which mucosal immunity would neutralize the mucosa invading pathogen before the onset of an infection. Hence, oral vaccination can eliminate the injection associated adverse effects and enhance the person's compliance. Conventional approaches to manufacturing oral vaccines, such as coacervation, spray drying, and membrane emulsification, tend to alter the structural proteins in vaccines that result from high temperature, organic and toxic solvents during production. Electrohydrodynamic processes, specifically electrospraying, could solve these challenges, as it also modulates antigen release and has a high loading efficiency. This review will highlight the mucosal immunity and biological basis of the gastrointestinal immune system, different oral vaccine delivery approaches, and the application of electrospraying in vaccines development. 相似文献
7.
Ellen K. Wasan Jaweria Syeda Stacy Strom Jacqueline Cawthray Robert E. Hancock Kishor M. Wasan Volker Gerdts 《Vaccine》2019,37(11):1503-1515
We previously developed an highly efficacious combination adjuvant comprised of innate defense regulator (IDR)-1002 peptide, poly(I:C) and polyphosphazene (TriAdj). Here we aimed to design and test the in vivo efficacy of a mucoadhesive nasal formulation of this adjuvant. To determine the physical properties of the formulation, the effect of addition of each individual component was characterised by gel electrophoresis and fluorescence quenching using rhodamine-poly(I:C). Cationic liposomes comprised of didodecyl dimethylammonium bromide (DDAB), dioleoyl phosphatidylethanolamine (DOPE) (50:50 or 75:25?mol:mol) and DDAB, L-α-phosphatidylcholine (egg PC) and DOPE (40:50:10?mol:mol:mol) were prepared by the thin-film extrusion method. The liposomes and TriAdj were combined by simple mixing. The formed complex (L-TriAdj) was characterized by dynamic light scattering, zeta potential, and mucin interactions. We found that IDR-1002 peptide, polyphosphazene and poly(I:C) self-assembled in solution forming an anionic complex. Exposure of RAW267.4 mouse macrophage cells to TriAdj alone vs. L-TriAdj indicated that DDAB/DOPE (50:50) and DDAB/EPC/cholesterol (40:50:10) complexation reduced TriAdj toxicity. Next, TriAdj-containing cationic liposomes were prepared at several molar ratios to determine optimal size, stability and desired positive charge. Transmission electron microscopy showed rearrangement of lipid structures on binding of liposomes to TriAdj and to mucin. Stable particles (<200?nm over 24?h) showed mucin binding of DDAB/DOPE?+?TriAdj was greater than DDAB/EPC/DOPE?+?TriAdj. To verify in vivo efficacy, mice were administered the DDAB/DOPE?+?TriAdj complex intranasally with ovalbumin as the antigen, and the immunogenic response was measured by ELISA (serum IgG1, IgG2a, IgA) and ELISpot assays (splenocyte IL-5, IFN-γ). Mice administered adjuvant showed a significantly greater immune response with L-TriAdj than TriAdj alone, with a dose-response proportionate to the triple adjuvant content, and an overall balanced Th1/Th2 immune response representing both systemic and mucosal immunity. 相似文献
8.
Mario Di Gioacchino Claudia Petrarca Alessia Gatta Gilda Scarano Anila Farinelli Loredana Della Valle 《Expert Review of Clinical Immunology》2020,16(5):513-525
ABSTRACT
Introduction
For several years now, medicine has been benefiting from the contribution of nanoparticles (NPs) technology for both diagnosis and therapy. They can be used as adjuvants, being capable per se of immune-modulating activity, or as carriers for molecules to be transported to a specific target, eventually loaded with specific ligands favoring specific uptake. 相似文献9.
10.
目的 研究不同分子量的三甲基壳聚糖(TMC)对载胰岛素口服纳米粒性质的影响,以寻找更适于口服的TMC分子量.方法 选用高、中、低分子量(400、200、50 kDa)的TMC为载体材料,采用离子交联法制备载胰岛素的聚电解质纳米粒;以不同分子量的TMC、三聚磷酸钠(TPP)和胰岛素(Ins)的浓度为考察因素,以纳米粒表面形态、粒径、Zeta电位、包封率和载药量为考察指标,进行单因素筛选试验,对比不同分子量的TMC对纳米粒性质的影响.结果与结论 中分子量TMC载胰岛素纳米粒的载药量较高,包封率合适,且释药较平稳,为相对较优的载体材料. 相似文献