全文获取类型
收费全文 | 1363篇 |
免费 | 62篇 |
出版年
2024年 | 2篇 |
2023年 | 3篇 |
2022年 | 10篇 |
2021年 | 28篇 |
2020年 | 8篇 |
2019年 | 22篇 |
2018年 | 31篇 |
2017年 | 24篇 |
2016年 | 37篇 |
2015年 | 49篇 |
2014年 | 59篇 |
2013年 | 76篇 |
2012年 | 116篇 |
2011年 | 118篇 |
2010年 | 72篇 |
2009年 | 60篇 |
2008年 | 99篇 |
2007年 | 103篇 |
2006年 | 85篇 |
2005年 | 69篇 |
2004年 | 78篇 |
2003年 | 71篇 |
2002年 | 57篇 |
2001年 | 11篇 |
2000年 | 7篇 |
1999年 | 7篇 |
1998年 | 12篇 |
1997年 | 13篇 |
1996年 | 11篇 |
1995年 | 9篇 |
1994年 | 7篇 |
1993年 | 5篇 |
1992年 | 9篇 |
1991年 | 7篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1985年 | 2篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1971年 | 2篇 |
1968年 | 2篇 |
1967年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有1425条查询结果,搜索用时 15 毫秒
41.
Sano Y Usami K Izawa R Denda-Nagai K Higashi N Kimura T Suzuki N Irimura T 《Journal of biochemistry》2007,141(1):127-136
Monoclonal antibodies (mAbs) specific for the human macrophage galactose-type calcium-type lectin (MGL) were established. The recombinant extracellular domain of MGL was used to immunize a mouse, and 10 hybridoma clones were obtained. Binding of recombinant MGL to asialo-bovine submaxillary mucin was shown to be blocked by mAbs MLD-1, 4 and 6. Immunoprecipitation of MGL from lysates of COS-1 cells transfected with MGL cDNA (form 6A) was achieved with mAbs MLD-1, 4, 7, 8 and 16. Chimeric recombinant proteins between human MGL and mouse MGL1 were used to determine the location of the epitopes for these mAbs. mAbs MLD-8, 13, 15 and 16 interacted with the amino terminal side of the conserved WVDGTD sequence immediately upstream of QPD, whereas mAbs MLD-7, 12 and 17 interacted with the other side. mAbs MLD-1, 4, and 6 apparently required both sides of this boundary. mAbs MLD-15 and 16 were shown to recognize the protein products of alternatively spliced mRNA 6A/8A and 6C/8A, having deletions at the boundary of exons 7 and 8, in addition to full length and other spliced forms of MGL (6A, 6B and 6C), whereas the other mAbs bound only full length and forms 6A, 6B and 6C. 相似文献
42.
Kaori Kurashima-Ito Kayano Moromisato Kaoru Nishimura Markus Wälchli Jeremy R. H. Tame Yutaka Ito 《Biomolecular NMR assignments》2007,1(1):37-39
Salmonella typhimurium OppA is the periplasmic oligopeptide-binding protein. Backbone resonances of OppA(D419N) on its own were assigned for ∼90%
of residues. Missing residues are localised around the ligand-binding site, suggesting conformational flexibility in the unliganded
state. 相似文献
43.
Hockemeyer D Palm W Else T Daniels JP Takai KK Ye JZ Keegan CE de Lange T Hammer GD 《Nature structural & molecular biology》2007,14(8):754-761
The shelterin complex at mammalian telomeres contains the single-stranded DNA-binding protein Pot1, which regulates telomere length and protects chromosome ends. Pot1 binds Tpp1, the shelterin component that connects Pot1 to the duplex telomeric DNA-binding proteins Trf1 and Trf2. Control of telomere length requires that Pot1 binds Tpp1 as well as the single-stranded telomeric DNA, but it is not known whether the protective function of Pot1 depends on Tpp1. Alternatively, Pot1 might function similarly to the Pot1-like proteins of budding and fission yeast, which have no known Tpp1-like connection to the duplex telomeric DNA. Using mutant mouse cells with diminished Tpp1 levels, RNA interference directed to mouse Tpp1 and Pot1, and complementation of mouse Pot1 knockout cells with human and mouse Pot1 variants, we show here that Tpp1 is required for the protective function of mammalian Pot1 proteins. 相似文献
44.
Nakahara M Nagasaka A Koike M Uchida K Kawane K Uchiyama Y Nagata S 《The FEBS journal》2007,274(12):3055-3064
The eye lens is composed of fiber cells that differentiate from epithelial cells on its anterior surface. In concert with this differentiation, a set of proteins essential for lens function is synthesized, and the cellular organelles are degraded. DNase II-like acid DNase, also called DNase IIbeta, is specifically expressed in the lens, and degrades the DNA in the lens fiber cells. Here we report that DNase II-like acid DNase is synthesized as a precursor with a signal sequence, and is localized to lysosomes. DNase II-like acid DNase mRNA was found in cortical fiber cells but not epithelial cells, indicating that its expression is induced during the differentiation of epithelial cells into fiber cells. Immunohistochemical and immunocytochemical analyses indicated that DNase II-like acid DNase was colocalized with Lamp-1 in the lysosomes of fiber cells in a relatively narrow region bordering the organelle-free zone, and was often found in degenerating nuclei. A comparison by microarray analysis of the gene expression profiles between epithelial and cortical fiber cells of young mouse lens indicated that some genes for lysosomal enzymes (cathepsins and lipases) were strongly expressed in the fiber cells. These results suggest that the lysosomal system plays a role in the degradation of cellular organelles during lens cell differentiation. 相似文献
45.
Kaori Tsutsumi Ayaka Chiba Yuta Tadaki Shima Minaki Takahito Ooshima Haruka Takahashi 《Current issues in molecular biology》2021,43(3):1203
Non-small cell lung cancer (NSCLC) is an aggressive lung cancer accounting for approximately 85% of all lung cancer patients. For the patients with Stages IIIA, IIIB, and IIIC, the 5-year survival is low though with the combination with radiotherapy and chemotherapy. In addition, the occurrence of tumor cells (repopulated tumors) that survive irradiation remains a challenge. In our previous report, we subcloned the radiation-surviving tumor cells (IR cells) using the human NSCLC cell line, H1299, and found that the expression of neuropilin-1 (NRP-1) was upregulated in IR cells by the microarray analysis. Here, we investigated the contribution of neuropilin-1 to changes in the characteristics of IR cells. Although there were no differences in angiogenic activity in the tube formation assay between parental and IR cells, the cell motility was increased in IR cells compared to parental cells in the cell migration assay. This enhanced cell motility was suppressed by pretreatment with anti-NRP-1 antibody. Although further studies are necessary to identify other molecules associated with NRP-1, the increase in cellular motility in IR cells might be due to the contribution of NRP-1. Inhibition of NRP-1 would help control tumor malignancy in radiation-surviving NSCLC. 相似文献
46.
Kaori Tsukakoshi Yasuko Yamagishi Mana Kanazashi Kenta Nakama Daiki Oshikawa Nasa Savory Akimasa Matsugami Fumiaki Hayashi Jinhee Lee Taiki Saito Koji Sode Kanjana Khunathai Hitoshi Kuno Kazunori Ikebukuro 《Nucleic acids research》2021,49(11):6069
Aptamers can control the biological functions of enzymes, thereby facilitating the development of novel biosensors. While aptamers that inhibit catalytic reactions of enzymes were found and used as signal transducers to sense target molecules in biosensors, no aptamers that amplify enzymatic activity have been identified. In this study, we report G-quadruplex (G4)-forming DNA aptamers that upregulate the peroxidase activity in myoglobin specifically for luminol. Using in vitro selection, one G4-forming aptamer that enhanced chemiluminescence from luminol by myoglobin''s peroxidase activity was discovered. Through our strategy—in silico maturation, which is a genetic algorithm-aided sequence manipulation method, the enhancing activity of the aptamer was improved by introducing mutations to the aptamer sequences. The best aptamer conserved the parallel G4 property with over 300-times higher luminol chemiluminescence from peroxidase activity more than myoglobin alone at an optimal pH of 5.0. Furthermore, using hemin and hemin-binding aptamers, we demonstrated that the binding property of the G4 aptamers to heme in myoglobin might be necessary to exert the enhancing effect. Structure determination for one of the aptamers revealed a parallel-type G4 structure with propeller-like loops, which might be useful for a rational design of aptasensors utilizing the G4 aptamer-myoglobin pair. 相似文献
47.
Ishikawa G Kanai Y Takata K Takeuchi R Shimanouchi K Ruike T Furukawa T Kimura S Sakaguchi K 《Nucleic acids research》2004,32(21):6251-6259
A novel endo-exonuclease, DmGEN (Drosophila Melanogaster XPG-like endonuclease), was identified in D.melanogaster. DmGEN is composed of five exons and four introns, and the open reading frame encodes a predicted product of 726 amino acid residues with a molecular weight of 82.5 kDa and a pI of 5.36. The gene locus on Drosophila polytene chromosomes was detected at 64C9 on the left arm of chromosome 3 as a single site. The encoded protein showed a relatively high degree of sequence homology with the RAD2 nucleases, especially XPG. Although the XPG-N- and XPG-I-domains are highly conserved in sequence, locations of the domains are similar to those of FEN-1 and EXO-1, and the molecular weight of the protein is close to that of EXO-1. In vitro, DmGEN showed endonuclease and 3'-5' exonuclease activities with both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), but the endonuclease action with dsDNA was quite specific: 5'-3' exonuclease activity was found to occur with nicked DNA, while dsDNA was endonucleolytically cut at 3-4 bp from the 5' end. Homologs are widely found in mammals and higher plants. The data suggest that DmGEN belongs to a new class of RAD2 nuclease. 相似文献
48.
Tomuro K 《Gerodontology》2004,21(3):177-180
Objectives: The aim of the pilot study was to develop and evaluate a telecare programme for home‐dwelling elderly to provide education on oral and general health care. Design: A field trial with a computer system linking a university with a structured network. Subjects: A group of home‐dwelling elderly males with a mean age of 73.3 years. Methods: Qualitative assessment following videophone interviews with clients and their families. Results: Clients and families were able to gain a better understanding and knowledge of oral health care particularly the skills required to perform new oral care procedures. Conclusions: Preventive oral homecare via videophone offers the potential for providing a long‐term structure for maintaining oral health particularly with limited social resources. 相似文献
49.
50.
In vivo monitoring of hydroxyl radical generation caused by x-ray irradiation of rats using the spin trapping/EPR technique 总被引:7,自引:0,他引:7
Measurement of hydroxyl radical (*OH) in living animals irradiated with ionizing radiation should be required to clarify the mechanisms of radiation injury and the in vivo assessment of radiation protectors, because generation of *OH is believed to be one of the major triggers of radiation injury. In this study, *OH generation was monitored by spin trapping the secondary methyl radical formed by the reaction of *OH with dimethyl sulfoxide (DMSO). Rats were injected intraperitoneally with a DMSO solution of alpha-phenyl-N-tert-butylnitrone (PBN). X-irradiation of the rats remarkedly increased the six-line EPR signal in the bile. The strengthened signal was detectable above 40 Gy. Use of 13C-substituted DMSO revealed that the signal included the methyl radical adduct of PBN as a major component. The EPR signal of the PBN-methyl radical adduct was completely suppressed by preadministration of methyl gallate, a scavenger of *OH but not of methyl radical. Methyl gallate did not reduce the spin adducts to EPR-silent forms. These observations indicate that what we were measuring was *OH generated in vivo by x-irradiation. This is the first report of the in vivo monitoring of *OH generation at a radiation dose close to what people might receive in the case of radiological accident or radiation therapy. 相似文献