收费全文 | 27718篇 |
免费 | 1767篇 |
国内免费 | 70篇 |
耳鼻咽喉 | 244篇 |
儿科学 | 617篇 |
妇产科学 | 496篇 |
基础医学 | 3901篇 |
口腔科学 | 642篇 |
临床医学 | 2575篇 |
内科学 | 5318篇 |
皮肤病学 | 475篇 |
神经病学 | 3064篇 |
特种医学 | 1123篇 |
外国民族医学 | 55篇 |
外科学 | 3834篇 |
综合类 | 359篇 |
一般理论 | 10篇 |
预防医学 | 2177篇 |
眼科学 | 784篇 |
药学 | 1920篇 |
中国医学 | 32篇 |
肿瘤学 | 1929篇 |
2022年 | 195篇 |
2021年 | 385篇 |
2020年 | 231篇 |
2019年 | 380篇 |
2018年 | 432篇 |
2017年 | 359篇 |
2016年 | 397篇 |
2015年 | 538篇 |
2014年 | 716篇 |
2013年 | 1067篇 |
2012年 | 1574篇 |
2011年 | 1631篇 |
2010年 | 894篇 |
2009年 | 833篇 |
2008年 | 1542篇 |
2007年 | 1651篇 |
2006年 | 1580篇 |
2005年 | 1602篇 |
2004年 | 1529篇 |
2003年 | 1434篇 |
2002年 | 1402篇 |
2001年 | 393篇 |
2000年 | 339篇 |
1999年 | 353篇 |
1998年 | 311篇 |
1997年 | 303篇 |
1996年 | 258篇 |
1995年 | 245篇 |
1994年 | 211篇 |
1993年 | 210篇 |
1992年 | 222篇 |
1991年 | 203篇 |
1990年 | 183篇 |
1989年 | 195篇 |
1988年 | 189篇 |
1987年 | 192篇 |
1986年 | 170篇 |
1985年 | 176篇 |
1984年 | 221篇 |
1983年 | 190篇 |
1982年 | 228篇 |
1981年 | 209篇 |
1980年 | 191篇 |
1979年 | 166篇 |
1978年 | 152篇 |
1977年 | 106篇 |
1976年 | 142篇 |
1975年 | 126篇 |
1974年 | 151篇 |
1973年 | 113篇 |
Objectives
Mechanical loading is a potential activator of inflammation and able to stimulate factors for periodontal and alveolar bone destruction. Aim of this study was to investigate the inflammatory response and synthesis of proteinases by human periodontal ligament fibroblast (HPdLF) dependent on different strengths of static tensile strain (STS).Materials and methods
HPdLFs were loaded with different STS strengths (1, 5, and 10 %) in vitro. Gene expressions of cyclooxygenase (COX)-2 and interleukin (IL)-6 were analyzed by quantitative real-time polymerase chain reaction. Production of IL-6, prostaglandin E2 (PGE2), matrix metalloproteinase (MMP)-8, and tissue inhibitors of matrix metalloproteinase (TIMP)-1 were measured by enzyme-linked immunosorbent assay. Receptor activator of nuclear factor-kappa ligand (RANKL) synthesis was detected by immunocytochemical staining.Results
Ten percent STS led to an increased gene expression of IL-6 and COX-2 (34.4-fold) in HPdLF, and 1 and 5 % STS slightly reduced the gene expression of IL-6. Synthesis of IL-6 was significantly reduced by 1 % STS and stimulated by 10 % STS. Ten percent STS significantly induced PGE2 production. RANKL was not detectable at any strength of STS. MMP-8 synthesis showed significantly higher values only at 10 % STS, but TIMP-1 was stimulated by 5 and 10 % STS, resulting into highest TIMP-1/MMP-8 ratio at 5 % STS.Conclusions
High-strength STS is a potent inducer of periodontal inflammation and MMP-8, whereas low-strength STS shows an anti-inflammatory effect. Moderate-strength STS causes the highest TIMP-1/MMP-8 ratio, leading to appropriate conditions for reformation of the extracellular matrix.Clinical relevance
Furthermore, this study points out that the strength of force plays a pivotal role to achieve orthodontic tooth movement without inducing periodontal inflammation and to activate extracellular matrix regeneration. 相似文献Objectives
The aim of this study was to evaluate the efficacy of four different powered toothbrushes with side-to-side action for noncontact biofilm removal in vitro.Materials and methods
A three-species biofilm was formed in vitro on protein-coated titanium disks using a flow chamber combined with a static biofilm growth model. Subsequently, the biofilm-coated substrates were exposed to four different side-to-side toothbrushes (A, B, C, and D) with various brushing times (2, 4, and 6 s) and brushing (bristle-to-disk) distances (0, 2, and 4 mm). The biofilm volumes were measured using volumetric analyses with confocal laser scanning microscope images and Imaris version 7.5.2 software.Results
The median percentages of biofilm reduction by the analyzed toothbrushes ranged from 9 % to 80 %. The abilities of the tested toothbrushes to remove the in vitro biofilm differed significantly (p?<?0.05). Two of the tested toothbrushes (C and D) were capable of significant biofilm reduction by noncontact brushing.Conclusions
It was possible to reduce a three-species in vitro biofilm by noncontact brushing with two out of four side-to-side toothbrushes.Clinical relevance
Toothbrushes C and D show in vitro a high efficacy in biofilm removal without bristle contact. 相似文献Extracellular vesicles, small vesicles carrying inter alia proteins, miRNA and RNA, are important mediators of intercellular communication. The purpose of this study was to assess the distribution of extracellular vesicles from highly malignant breast cancer and their subsequent effect on the immune cell infiltrate in target organs of metastasis.
ProceduresExtracellular vesicles were isolated from the tissue culture supernatant of highly malignant 4T1 breast cancer cells or the serum of healthy BALB/c mice. The purity of the isolate was verified by electron microscopy and western blotting. Extracellular vesicles were additionally subjected to proteome analysis. After labeling with the fluorescent dye DiR, extracellular vesicles were injected into healthy BALB/c mice and their in vivo distribution was assessed using fluorescence reflectance imaging (FRI). Following ex vivo imaging of the organs, lung tissue samples were analyzed for extracellular vesicle-mediated changes of myeloid cells and T cell numbers, using flow cytometry. Proteome analysis revealed major differences in the cargo of tumor cell–derived versus extracellular vesicles from healthy serum.
ResultsIn contrast to control extracellular vesicles, DiR-labeled extracellular vesicles from tumor cells preferentially accumulated in lung, liver, and spine. Subsequent flow cytometry of the immune cell composition of lung tissue samples revealed an increase of cytotoxic CD8+ T cells and a decrease of CD4+ T-helper cells as well as an increase in mature macrophages in response to tumor cell EV.
ConclusionsIn conclusion, distribution of tumor cell–derived extracellular vesicles follows a specific pattern and can be monitored, using dedicated imaging. Extracellular vesicles alter the immune cell composition in target organs of metastasis, using a specific proteome cargo.
相似文献- WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
- WHAT QUESTION DID THIS STUDY ADDRESS?
- WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
- HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?