全文获取类型
收费全文 | 4465篇 |
免费 | 344篇 |
国内免费 | 527篇 |
专业分类
5336篇 |
出版年
2024年 | 11篇 |
2023年 | 57篇 |
2022年 | 182篇 |
2021年 | 270篇 |
2020年 | 202篇 |
2019年 | 235篇 |
2018年 | 217篇 |
2017年 | 167篇 |
2016年 | 240篇 |
2015年 | 315篇 |
2014年 | 418篇 |
2013年 | 363篇 |
2012年 | 476篇 |
2011年 | 431篇 |
2010年 | 284篇 |
2009年 | 239篇 |
2008年 | 266篇 |
2007年 | 218篇 |
2006年 | 138篇 |
2005年 | 138篇 |
2004年 | 91篇 |
2003年 | 82篇 |
2002年 | 49篇 |
2001年 | 37篇 |
2000年 | 28篇 |
1999年 | 21篇 |
1998年 | 7篇 |
1997年 | 9篇 |
1996年 | 7篇 |
1995年 | 8篇 |
1994年 | 6篇 |
1993年 | 3篇 |
1992年 | 12篇 |
1991年 | 9篇 |
1990年 | 9篇 |
1989年 | 11篇 |
1988年 | 5篇 |
1987年 | 8篇 |
1986年 | 12篇 |
1985年 | 11篇 |
1984年 | 5篇 |
1983年 | 8篇 |
1982年 | 3篇 |
1980年 | 7篇 |
1978年 | 4篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1958年 | 1篇 |
1956年 | 1篇 |
排序方式: 共有5336条查询结果,搜索用时 15 毫秒
11.
Wei-liang Ye Jiang-bo Du Bang-le Zhang Ren Na Yan-feng Song Qi-bing Mei Ming-gao Zhao Si-yuan Zhou 《PloS one》2014,9(5)
A PEG-based, folate mediated, active tumor targeting drug delivery system using DOX-hyd-PEG-FA nanoparticles (NPs) were prepared. DOX-hyd-PEG-FA NPs showed a significantly faster DOX release in pH 5.0 medium than in pH 7.4 medium. Compared with DOX-hyd-PEG NPs, DOX-hyd-PEG-FA NPs increased the intracellular accumulation of DOX and showed a DOX translocation from lysosomes to nucleus. The cytotoxicity of DOX-hyd-PEG-FA NPs on KB cells was much higher than that of free DOX, DOX-ami-PEG-FA NPs and DOX-hyd-PEG NPs. The cytotoxicity of DOX-hyd-PEG-FA NPs on KB cells was attenuated in the presence of exogenous folic acid. The IC50 of DOX-hyd-PEG-FA NPs and DOX-hyd-PEG NPs on A549 cells showed no significant difference. After DOX-hyd-PEG-FA NPs were intravenously administered, the amount of DOX distributed in tumor tissue was significantly increased, while the amount of DOX distributed in heart was greatly decreased as compared with free DOX. Compared with free DOX, NPs yielded improved survival rate, prolonged life span, delayed tumor growth and reduced the cardiotoxicity in tumor bearing mice model. These results indicated that the acid sensitivity, passive and active tumor targeting abilities were likely to act synergistically to enhance the drug delivery efficiency of DOX-hyd-PEG-FA NPs. Therefore, DOX-hyd-PEG-FA NPs are a promising drug delivery system for targeted cancer therapy. 相似文献
12.
The Hfq protein is reported to be an RNA chaperone, which is involved in the stress response and the virulence of several pathogens. In E. coli, Hfq can mediate the interaction between some sRNAs and their target mRNAs. But it is controversial whether Hfq plays an important role in S. aureus. In this study, we found that the deletion of hfq gene in S. aureus 8325-4 can increase the surface carotenoid pigments. The hfq mutant was more resistant to oxidative stress but the pathogenicity of the mutant was reduced. We reveal that the Hfq protein can be detected only in some S. aureus strains. Using microarray and qRT-PCR, we identified 116 genes in the hfq mutant which had differential expression from the wild type, most of which are related to the phenotype and virulence of S. aureus. Among the 116 genes, 49 mRNAs can specifically bind Hfq protein, which indicates that Hfq also acts as an RNA binding protein in S. aureus. Our data suggest that Hfq protein of S. aureus is a multifunctional regulator involved in stress and virulence. 相似文献
13.
Background
Interleukin-35 (IL-35) has recently been identified as an immunosuppressive cytokine that has been used as a potential therapy for chronic inflammatory and autoimmune diseases. However, there remains a paucity of data regarding its potential benefits after integration into mesenchymal stem cells (MSCs).Methods
We used a dextran sulfate sodium (DSS)–induced colitis mice model and treated them with IL-35-MSCs, MSCs or saline. The body weight was recorded daily and inflammatory processes were determined. Cytokine secretion by lamina propria lymphocytes (LPLs) and percentage of regulatory T cells (Tregs) were also measured.Results
The data showed that mice in the two treated groups recovered their body weight more rapidly than mice treated with saline in the later stage of colitis. The colon lengths of IL-35-MSC–treated mice were markedly longer than those in the other two groups and the inflammation reduced significantly. Furthermore, the percentage of Foxp3?+?Tregs increased significantly and the level of proinflammatory cytokines produced by LPLs decreased significantly in the IL-35-MSC–treated group.Discussion
The results demonstrate that IL-35-MSCs could ameliorate ulcerative colitis by down-regulating the expression of pro-inflammatory cytokines. 相似文献14.
15.
Seong-In Na Yeong Ouk Kim Seok-Hwan Yoon Sung-min Ha Inwoo Baek Jongsik Chun 《Journal of microbiology (Seoul, Korea)》2018,56(4):280-285
Genome-based phylogeny plays a central role in the future taxonomy and phylogenetics of Bacteria and Archaea by replacing 16S rRNA gene phylogeny. The concatenated core gene alignments are frequently used for such a purpose. The bacterial core genes are defined as single-copy, homologous genes that are present in most of the known bacterial species. There have been several studies describing such a gene set, but the number of species considered was rather small. Here we present the up-to-date bacterial core gene set, named UBCG, and software suites to accommodate necessary steps to generate and evaluate phylogenetic trees. The method was successfully used to infer phylogenomic relationship of Escherichia and related taxa and can be used for the set of genomes at any taxonomic ranks of Bacteria. The UBCG pipeline and file viewer are freely available at https://www.ezbiocloud.net/tools/ubcg and https://www.ezbiocloud.net/tools/ubcg_viewer, respectively. 相似文献
16.
Yunlong Wang Shulai Lu Xinde Li Na Du Yunbo Sun Jinyan Xing Xinting Pan Baosheng Chen Zhimin Miao 《PloS one》2012,7(12)
Our previous studies showed that recombinant high-density lipoprotein (rHDL) rHDL74 exhibited higher anti-inflammatory capabilities compared to wild-type rHDL (rHDLwt), while rHDL228 showed hyper-proinflammation. In this paper, we further investigated the potential mechanisms involved in their different inflammatory functions using two models: endotoxemic mice and the RAW264.7 inflammation model. Our results showed that 24 h after the injection of lipopolysaccharide (LPS), mice treated with rHDL74 had a significant decrease in plasma CRP (P<0.01 vs. rHDLwt; P<0.01 vs. LPS), MCP-1 (P<0.05 vs. rHDLwt; P<0.01 vs. LPS) and CD14 (P<0.01 vs. LPS) compared with the mice treated with rHDLwt or the controls that received LPS only. Similar to our previous study, rHDL228 increased the plasma level of CRP (P<0.05 vs. LPS) and MCP-1 (P<0.01 vs. LPS). Our immunohistochemistry and western blot analysis showed that rHDL74 inhibited the activation of NF-κB in endotoxemic mice and JNK and p38 in the RAW264.7 inflammation model, while rHDL228 exacerbated the activation of NF-κB and ERK. In summary, our data suggest that rHDL74 exhibits higher anti-inflammatory activity by decreasing inflammatory factors and inhibiting the activation of NF-κB, JNK and p38, while rHDL228 appears to be hyper-proinflammation by increasing these inflammatory factors and aggravating the activation of NF-κB and ERK. 相似文献
17.
18.
19.
The objective of this study was to investigate the difference in electrophoretic mobility between partially and fully poly(ethylene glycol)-conjugated poly(amidoamine) dendrimers (part-PEG-PAMAM and full-PEG-PAMAM, respectively) using a microchip capillary gel electrophoresis (MCGE). While MCGE allowed size-based separation of PEG-PAMAMs prepared with monomethoxy PEG-nitrophenyl carbonate, full-PEG-PAMAMs migrated slower than part-PEG-PAMAMs that were similar in size or larger. When the measured molecular weights obtained from MCGE analysis and the calculated molecular weights were plotted, each part-PEG-PAMAM and full-PEG-PAMAM showed correlation coefficients greater than 0.98. This study indicates that MCGE would be useful for characterizing PEG-PAMAMs with different PEGylation degrees. 相似文献
20.
Renal cell carcinoma (RCC) is one of the most common malignancies in the urinary system. Due to the lack of early symptoms, diagnosis of RCC usually occurs at late stages or after cancer metastasis leading to poor prognosis. Therefore, it is crucial to study early molecular mechanisms and biomarkers. Previous studies have suggested that microRNAs are involved in RCC initiation and development, making them a good candidate for early diagnosis and therapy. MiR146b-5P plays important roles in the progression of multiple cancers including thyroid cancer, pancreatic cancer, cervical cancer. However, it is not clear whether and how miR146b-5P is involved in RCC. In this study, we aimed to investigate the function of miR146b-5P in RCC. We examined the expression levels of miR146b-5p in renal cancer tissue and cell lines. We also explored the effects of blocking miR146b-5p in renal tumor growth and inflammatory signaling. Finally, we determined if miR146b-5p regulates tumorigenesis through TRAF6. We found that miR146b-5p levels were significantly increased in renal cancer tissue and renal cancer cells. Blocking miR146b-5p suppressed renal tumor growth and enhanced inflammatory response through increased TRAF6 expression. These effects were eliminated in TRAF6 knockout mice. Our results suggest that enhanced miR146b-5p expression may be a biomarker for RCC and modulating miR146b-5p and TRAF6 levels represent a potential therapeutic strategy for RCC. 相似文献