全文获取类型
收费全文 | 1796篇 |
免费 | 136篇 |
国内免费 | 202篇 |
出版年
2024年 | 1篇 |
2023年 | 22篇 |
2022年 | 51篇 |
2021年 | 94篇 |
2020年 | 68篇 |
2019年 | 95篇 |
2018年 | 84篇 |
2017年 | 61篇 |
2016年 | 89篇 |
2015年 | 114篇 |
2014年 | 130篇 |
2013年 | 143篇 |
2012年 | 152篇 |
2011年 | 134篇 |
2010年 | 86篇 |
2009年 | 84篇 |
2008年 | 102篇 |
2007年 | 77篇 |
2006年 | 82篇 |
2005年 | 68篇 |
2004年 | 63篇 |
2003年 | 45篇 |
2002年 | 42篇 |
2001年 | 37篇 |
2000年 | 35篇 |
1999年 | 35篇 |
1998年 | 17篇 |
1997年 | 13篇 |
1996年 | 15篇 |
1995年 | 15篇 |
1994年 | 10篇 |
1993年 | 9篇 |
1992年 | 10篇 |
1991年 | 9篇 |
1990年 | 11篇 |
1989年 | 5篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1986年 | 6篇 |
1985年 | 7篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1980年 | 1篇 |
排序方式: 共有2134条查询结果,搜索用时 15 毫秒
31.
Abstract A novel approach to 2′-O-alkylpyrimidine nucleosides involving a 3′- hydroxyl assisted intramolecular delivery of a divalent metal alkoxide leads to a regiospecific opening of the anhydropyrimidine linkage at the 2′-position. Thus, reaction of 5′-protected 2,2′-anhydrouridine with magnesium or calcium alkoxides in DMF affords exclusively the corresponding 2′-O-alkyluridines in reasonable yields. 相似文献
32.
Xia Qin Zhen-Quan Sun Xue-Wei Zhang Xiao-Jing Dai Shan-Shan Mao Yong-Mei Zhang 《Journal of physiology and biochemistry》2013,69(4):707-718
Propofol exhibits neuroprotective effects against hypoxic–ischemic brain injury, but the underlying mechanisms are still not clear. Toll-like receptor 4 (TLR4) plays a considerable role in the induction of innate immune and inflammatory responses. The purposes of this study are to investigate the effect of propofol on the oxygen and glucose deprivation (OGD)/reoxygenation (OGD/R) BV2 microglia and to explore the role of TLR4/myeloid differentiation protein 88 (MyD88)/nuclear factor-kappa B (NF-κB) pathway in the neuroprotective effects of propofol. BV2 microglia were placed into an airtight chamber and in glucose-free medium for OGD/reoxygenation. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay. TLR4 and its downstream signaling molecules, MyD88 and NF-κB expressions were detected by Western blotting. Level of tumor necrosis factor alpha (TNF-α) in culture medium was determined with enzyme-linked immunosorbent assay. BV2 microglia apoptosis was determined by flow cytometry. We found that pretreatment with propofol significantly alleviated the hypoxic injury in BV2 microglia. Propofol inhibited upregulation of TLR4, MyD88, and NF-κB expressions in BV2 microglia exposed to OGD/reoxygenation. Propofol pretreatment also significantly reduced the production of TNF-α and apoptosis in OGD/reoxygenation BV2 microglia. The results indicated that TLR4 and its downstream MyD88-dependent signaling pathway contributed to neuroprotection of propofol to microglia exposed to OGD/reoxygenation. 相似文献
33.
Background
Xenotransplantation is a promising approach to circumventing the current organ shortage. However, T-cell-dependent anti-xenoresponses are a major challenge to successful xenografts. Given the advantages of the use of CTLA4-Ig in the survival of allografts, the purpose of the study was to investigate the therapeutic potential of CTLA4-IgG4 modified immature dendritic cells (imDCs) in the prevention of islets xenograft rejection.Methods
CTLA4-IgG4 was constructed by the fusion of the extracellular regions of porcine CTLA4 to human the hIgG4 Fc region. The imDCs were induced and cultured from porcine peripheral blood mononuclear cells (PBMC). The CTLA4-IgG4 modified imDCs were delivered via the portal vein to the liver of diabetic mice (insulin-dependent diabetes mellitus) before islet xenografting, and mCTLA4-Ig was administered intravenously after xenotransplantation.Results
The xenograft survival of mice receiving unmodified imDCs was approximately 30 days. However, following administration of CTLA4-IgG4 modified imDCs before grafting and mCTLA4-Ig after grafting, xenografts survived for more than 100 days. Flow cytometric analysis showed that the CD4+CD25+Foxp3+ Treg population was increased in spleens. The efficacy of donor CTLA4-IgG4 modified imDCs correlated partially with the amplification of Tregs.Conclusions
These results confirm that selective inhibition of the direct and indirect pathways of T-cell activation by donor CTLA4-IgG4 modified imDCs and receptor CTLA4-Ig is a highly effective strategy to promote survival of xenografts. 相似文献34.
35.
Linhui Zhai Cheng Chang Ning Li Duc M. Duong Hao Chen Zixin Deng Jian Yang Xuechuan Hong Yunping Zhu Ping Xu 《Proteomics》2013,13(15):2229-2237
Reversed phase microcolumns have been widely used for peptide pretreatment to desalt and remove interferences before tandem LC–MS in proteomics studies. However, few studies have characterized the effects of experimental parameters as well as column characteristics on the composition of identified peptides. In this study, several parameters including the concentration of ACN in washing buffer, the microcolumn's purification effect, the peptide recovery rate, and the dynamic‐binding capacity were characterized in detail, based upon stable isotope labeling by amino acids in a cell culture quantitative approach. The results showed that peptide losses can be reduced with low ACN concentration in washing buffers resulting in a recovery rate of approximately 82%. Furthermore, the effects of ACN concentration and loading amount on the properties of identified peptides were also evaluated. We found that the dynamic‐binding capacity of the column was approximately 26 μg. With increased loading amounts, more hydrophilic peptides were replaced by hydrophobic peptides. 相似文献
36.
Liuhua Yan Qingzhe Zhai Jianing Wei Shuyu Li Bao Wang Tingting Huang Minmin Du Jiaqiang Sun Le Kang Chang-Bao Li Chuanyou Li 《PLoS genetics》2013,9(12)
In response to insect attack and mechanical wounding, plants activate the expression of genes involved in various defense-related processes. A fascinating feature of these inducible defenses is their occurrence both locally at the wounding site and systemically in undamaged leaves throughout the plant. Wound-inducible proteinase inhibitors (PIs) in tomato (Solanum lycopersicum) provide an attractive model to understand the signal transduction events leading from localized injury to the systemic expression of defense-related genes. Among the identified intercellular molecules in regulating systemic wound response of tomato are the peptide signal systemin and the oxylipin signal jasmonic acid (JA). The systemin/JA signaling pathway provides a unique opportunity to investigate, in a single experimental system, the mechanism by which peptide and oxylipin signals interact to coordinate plant systemic immunity. Here we describe the characterization of the tomato suppressor of prosystemin-mediated responses8 (spr8) mutant, which was isolated as a suppressor of (pro)systemin-mediated signaling. spr8 plants exhibit a series of JA-dependent immune deficiencies, including the inability to express wound-responsive genes, abnormal development of glandular trichomes, and severely compromised resistance to cotton bollworm (Helicoverpa armigera) and Botrytis cinerea. Map-based cloning studies demonstrate that the spr8 mutant phenotype results from a point mutation in the catalytic domain of TomLoxD, a chloroplast-localized lipoxygenase involved in JA biosynthesis. We present evidence that overexpression of TomLoxD leads to elevated wound-induced JA biosynthesis, increased expression of wound-responsive genes and, therefore, enhanced resistance to insect herbivory attack and necrotrophic pathogen infection. These results indicate that TomLoxD is involved in wound-induced JA biosynthesis and highlight the application potential of this gene for crop protection against insects and pathogens. 相似文献
37.
Xue Wang Fengting Xu Jiasen Liu Bingquan Gao Yanxin Liu Yujia Zhai Jun Ma Kai Zhang Timothy S. Baker Klaus Schulten Dong Zheng Hai Pang Fei Sun 《PLoS pathogens》2013,9(1)
Rabbit hemorrhagic disease, first described in China in 1984, causes hemorrhagic necrosis of the liver. Its etiological agent, rabbit hemorrhagic disease virus (RHDV), belongs to the Lagovirus genus in the family Caliciviridae. The detailed molecular structure of any lagovirus capsid has yet to be determined. Here, we report a cryo-electron microscopic (cryoEM) reconstruction of wild-type RHDV at 6.5 Å resolution and the crystal structures of the shell (S) and protruding (P) domains of its major capsid protein, VP60, each at 2.0 Å resolution. From these data we built a complete atomic model of the RHDV capsid. VP60 has a conserved S domain and a specific P2 sub-domain that differs from those found in other caliciviruses. As seen in the shell portion of the RHDV cryoEM map, which was resolved to ∼5.5 Å, the N-terminal arm domain of VP60 folds back onto its cognate S domain. Sequence alignments of VP60 from six groups of RHDV isolates revealed seven regions of high variation that could be mapped onto the surface of the P2 sub-domain and suggested three putative pockets might be responsible for binding to histo-blood group antigens. A flexible loop in one of these regions was shown to interact with rabbit tissue cells and contains an important epitope for anti-RHDV antibody production. Our study provides a reliable, pseudo-atomic model of a Lagovirus and suggests a new candidate for an efficient vaccine that can be used to protect rabbits from RHDV infection. 相似文献
38.
Four trinorsesquiterpenoids (1–4) were isolated from the roots of Inula racemosa and the structures of two new compounds, (4R,5S,10S)-5-hydroxy-11,12,13-trinoreudesm-6-en-8-one (1) and (4R,5R,10R)-4,15-epoxy-11,12,13-trinoreudesman-8-one (3), were elucidated by extensive spectroscopic analysis. Furthermore, the structure of compound 2a should be revised as (4R,5R,10S)-5-hydroxy-11,12,13-trinoreudesm-6-en-8-one (2) and compound 2 showed antiproliferative activity against A549, HepG2, and HT1080 cell lines with IC50 values of 3.71, 5.94, and 3.95 μg/mL, respectively. 相似文献
39.
40.
Guo-Qiang Zhang Ke-Wei Liu Li-Jun Chen Xin-Ju Xiao Jun-Wen Zhai Li-Qiang Li Jing Cai Yu-Yun Hsiao Wen-Hui Rao Jie Huang Xue-Yong Ma Shih-Wen Chung Lai-Qiang Huang Wen-Chieh Tsai Zhong-Jian Liu 《PloS one》2013,8(4)