全文获取类型
收费全文 | 7060篇 |
免费 | 733篇 |
国内免费 | 1145篇 |
出版年
2024年 | 26篇 |
2023年 | 106篇 |
2022年 | 218篇 |
2021年 | 394篇 |
2020年 | 290篇 |
2019年 | 376篇 |
2018年 | 356篇 |
2017年 | 281篇 |
2016年 | 307篇 |
2015年 | 451篇 |
2014年 | 539篇 |
2013年 | 589篇 |
2012年 | 669篇 |
2011年 | 585篇 |
2010年 | 424篇 |
2009年 | 355篇 |
2008年 | 417篇 |
2007年 | 370篇 |
2006年 | 319篇 |
2005年 | 307篇 |
2004年 | 280篇 |
2003年 | 264篇 |
2002年 | 249篇 |
2001年 | 142篇 |
2000年 | 134篇 |
1999年 | 110篇 |
1998年 | 73篇 |
1997年 | 77篇 |
1996年 | 57篇 |
1995年 | 41篇 |
1994年 | 40篇 |
1993年 | 27篇 |
1992年 | 16篇 |
1991年 | 10篇 |
1990年 | 9篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1987年 | 7篇 |
1985年 | 4篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 5篇 |
1981年 | 1篇 |
排序方式: 共有8938条查询结果,搜索用时 15 毫秒
171.
Shengman Wang Lihong Wang Qing Zhou Xiaohua Huang 《Biological trace element research》2013,156(1-3):298-307
Heavy metal pollution and soil acidification are serious global environmental issues. The combined pollution from acidification and heavy metal has become a new environmental issue in regions where the two issues simultaneously occur. However, studies on combined pollution are still limited. In the current study, we investigated the combined effect and mechanism of acidity and heavy metal [lead ion (Pb2+)] on soybean biomass as well as on growth, nitrogen nutrition, and antioxidant system in soybean roots. Results showed that the combined treatment with acidity and Pb2+ decreased the soybean biomass. At pH 4.5, the soybean biomass in the combined treatment with acidity and 0.9 mmol L?1 Pb2+ was lower than that in the combined treatment with acidity and Pb2+ at 0.3 or 1.5 mmol L?1. This result was also observed at pH 3.5 and 3.0. The combined treatment with acidity and Pb2+ also resulted in the following consequences: root growth inhibition; decrease in nitrate, ammonium, and malondialdehyde contents; increase in nitrite reductase activity; and decrease in peroxidase activity. The extent at which the test indexes decreased/increased in the combined treatment was higher than that in the single acidity treatment. The correlation analysis results indicated that the decrease in the soybean biomass in the combined treatment with acidity and Pb2+ resulted from the decrease in the root growth, nitrate–nitrogen assimilation, and peroxidase activity. 相似文献
172.
Mingsong Kang Ya-Ping Ko Xiaowen Liang Caná L. Ross Qing Liu Barbara E. Murray Magnus H??k 《The Journal of biological chemistry》2013,288(28):20520-20531
Members of a family of collagen-binding microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) from Gram-positive bacteria are established virulence factors in several infectious diseases models. Here, we report that these adhesins also can bind C1q and act as inhibitors of the classical complement pathway. Molecular analyses of Cna from Staphylococcus aureus suggested that this prototype MSCRAMM bound to the collagenous domain of C1q and interfered with the interactions of C1r with C1q. As a result, C1r2C1s2 was displaced from C1q, and the C1 complex was deactivated. This novel function of the Cna-like MSCRAMMs represents a potential immune evasion strategy that could be used by numerous Gram-positive pathogens. 相似文献
173.
Jingjing Ben Yan Zhang Rongmei Zhou Haiyang Zhang Xudong Zhu Xiaoyu Li Hanwen Zhang Nan Li Xiaodan Zhou Hui Bai Qing Yang Donghai Li Yong Xu Qi Chen 《The Journal of biological chemistry》2013,288(27):20076-20084
Atherosclerosis is considered a disease of chronic inflammation largely initiated and perpetuated by macrophage-dependent synthesis and release of pro-inflammatory mediators. Class A scavenger receptor (SR-A) expressed on macrophages plays a key role in this process. However, how SR-A-mediated pro-inflammatory response is modulated in macrophages remains ill defined. Here through immunoprecipitation coupled with mass spectrometry, we reported major vault protein (MVP) as a novel binding partner for SR-A. The interaction between SR-A and MVP was confirmed by immunofluorescence staining and chemical cross-linking assay. Treatment of macrophages with fucoidan, a SR-A ligand, led to a marked increase in TNF-α production, which was attenuated by MVP depletion. Further analysis revealed that SR-A stimulated TNF-α synthesis in macrophages via the caveolin- instead of clathrin-mediated endocytic pathway linked to p38 and JNK, but not ERK, signaling pathways. Importantly, fucoidan invoked an enrichment of MVP in lipid raft, a caveolin-reliant membrane structure, and enhanced the interaction among SR-A, caveolin, and MVP. Finally, we demonstrated that MVP elimination ameliorated SR-A-mediated apoptosis in macrophages. As such, MVP may fine-tune SR-A activity in macrophages which contributes to the development of atherosclerosis. 相似文献
174.
Qing Deng Huiling Zhang Ruirui Xiang Zhenwu Zhang Fei Ling Min Zhuo Hongli Du Xiaoning Wang 《Immunogenetics》2013,65(12):901-904
Rhesus macaques have long been used as animal models for various human diseases; the susceptibility and/or resistance to some of these diseases are related to the major histocompatibility complex (MHC). To gain insight into the MHC background and to facilitate the experimental use of Chinese rhesus macaques, Mamu-DPA1, Mamu-DQA1, and Mamu-DRA alleles were investigated in 30 Chinese rhesus macaques by gene cloning and sequencing. A total of 14 Mamu-DPA1, 17 Mamu-DQA1, and 9 Mamu-DRA alleles were identified in this study. Of these alleles, 22 novel sequences have not been documented in earlier studies, including nine Mamu-DPA1, ten Mamu-DQA1, and three Mamu-DRA alleles. Interestingly, like Mafa-DQA1 and Mafa-DPA1, more than two Mamu-DQA1 and Mamu-DPA1 alleles were detected in one animal in this study, which suggested that they might represent gene duplication. If our findings can be validated by other studies, it will further increase the number of known Mamu-DPA1 and Mamu-DQA1 polymorphisms. Our data also indicated significant differences in MHC class II allele distribution among the Chinese rhesus macaques, Vietnamese cynomolgus macaques, and the previously reported rhesus macaques, which were mostly of Indian origin. This information will not only promote the understanding of Chinese rhesus macaque MHC diversity and polymorphism but will also facilitate the use of Chinese rhesus macaques in studies of human disease. 相似文献
175.
Fengqiong Liu Qing Lv William W. Du Haoran Li Xiangling Yang Danyang Liu Zhaoqun Deng Wenhua Ling Yaou Zhang Burton B. Yang 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2013,1833(12):3272-3285
One criterion for microRNA identification is based on their conservation across species, and prediction of miRNA targets by empirical approaches using computational analysis relies on the presence of conservative mRNA 3′UTR. Because most miRNA target sites identified are highly conserved across different species, it is not clear whether miRNA targeting is species-specific. To predict miRNA targeting, we aligned all available fibronectin 3′UTRs and observed significant conservation of all 20 species. Twelve miRNAs were predicted to target most fibronectin 3′UTRs, but rodent fibronectin showed potential binding sites specific for five different miRNAs. One of them, the miR-378a-5p, contained a complete matching seed-region for all rodent fibronectin, which could not be found in any other species. We designed experiments to test whether the species-specific targeting possessed biological function and found that expression of miR-378a-5p decreased cancer cell proliferation, migration, and invasion, resulting in inhibition of tumor growth. Silencing fibronectin expression produced similar effects as miR-378a-5p, while transfection with a construct targeting miR-378-5p produced opposite results. Tumor formation assay showed that enhanced expression of fibronectin in the stromal tissues as a background environment suppressed tumor growth, while increased fibronectin expression inside the tumor cells promoted tumor growth. This was likely due to the different signaling direction, either inside-out or outside-in signal. Our results demonstrated that species-specific targeting by miRNA could also exert functional effects. Thus, one layer of regulation has been added to the complex network of miRNA signaling. 相似文献
176.
Liping Zhang Hong Zhang Yining Zhao Zhe Li Shangke Chen Jing Zhai Yunyun Chen Wei Xie Zhong Wang Qing Li Xuehua Zheng Xiaopeng Hu 《FEBS letters》2013
The antineoplastic target aldo–keto reductase family member 1B10 (AKR1B10) and the critical polyol pathway enzyme aldose reductase (AKR1B1) share high structural similarity. Crystal structures reported here reveal a surprising Trp112 native conformation stabilized by a specific Gln114-centered hydrogen bond network in the AKR1B10 holoenzyme, and suggest that AKR1B1 inhibitors could retain their binding affinities toward AKR1B10 by inducing Trp112 flip to result in an “AKR1B1-like” active site in AKR1B10, while selective AKR1B10 inhibitors can take advantage of the broader active site of AKR1B10 provided by the native Trp112 side-chain orientation. 相似文献
177.
Tao Fang Wang Heng Wang Ai Fen Peng Qing Feng Luo Zhi Li Liu Rong Ping Zhou Song Gao Yang Zhou Wen Zhao Chen 《Biochemical and biophysical research communications》2013
FASN plays an important role in the malignant phenotype of various tumors. Our previous studies show that inhibition FASN could induce apoptosis and inhibit proliferation in human osteosarcoma (OS) cell in vivo and vitro. The aim in this study was to investigate the effect of inhibition FASN on the activity of HER2/PI3K/AKT axis and invasion and migration of OS cell. The expression of FASN, HER2 and p-HER2(Y1248) proteins was detected by immunohistochemistry in OS tissues from 24 patients with pulmonary metastatic disease, and the relationship between FASN and p-HER2 as well as HER2 was investigated. The results showed that there was a positive correlation between FASN and HER2 as well as p-HER2 protein expression. The U-2 OS cells were transfected with either the FASN specific RNAi plasmid or the negative control RNAi plasmid. FASN mRNA was measured by RT-PCR. Western blot assays was performed to examine the protein expression of FASN, HER2, p-HER2(Y1248), PI3K, Akt and p-Akt (Ser473). Migration and invasion of cells were investigated by wound healing and transwell invasion assays. The results showed that the activity of HER2/PI3K/AKT signaling pathway was suppressed by inhibiting FASN. Meanwhile, the U-2OS cells migration and invasion were also impaired by inhibiting the activity of FASN/HER2/PI3K/AKT. Our results indicated that inhibition of FASN suppresses OS cell invasion and migration via down-regulation of the “HER2/PI3K/AKT” axis in vitro. FASN blocker may be a new therapeutic strategy in OS management. 相似文献
178.
Pin Guo Quanmin Nie Jin Lan Jianwei Ge Yongming Qiu Qing Mao 《Biochemical and biophysical research communications》2013
The c-Myc oncogene is amplified in many tumor types. It is an important regulator of cell proliferation and has been linked to altered miRNA expression, suggesting that c-Myc-regulated miRNAs might contribute to tumor progression. Although miR-26a has been reported to be upregulated in glioblastoma multiforme (GBM), the mechanism has not been established. We have shown that ectopic expression of miR-26a influenced cell proliferation by targeting PTEN, a tumor suppressor gene that is inactivated in many common malignancies, including GBM. Our findings suggest that c-Myc modulates genes associated with oncogenesis in GBM through deregulation of miRNAs via the c-Myc–miR-26a–PTEN signaling pathway. This may be of clinical relevance. 相似文献
179.