全文获取类型
收费全文 | 875篇 |
免费 | 64篇 |
出版年
2023年 | 4篇 |
2022年 | 14篇 |
2021年 | 28篇 |
2020年 | 12篇 |
2019年 | 13篇 |
2018年 | 21篇 |
2017年 | 16篇 |
2016年 | 32篇 |
2015年 | 35篇 |
2014年 | 43篇 |
2013年 | 47篇 |
2012年 | 53篇 |
2011年 | 85篇 |
2010年 | 47篇 |
2009年 | 36篇 |
2008年 | 53篇 |
2007年 | 55篇 |
2006年 | 47篇 |
2005年 | 42篇 |
2004年 | 27篇 |
2003年 | 29篇 |
2002年 | 17篇 |
2001年 | 10篇 |
2000年 | 8篇 |
1999年 | 12篇 |
1997年 | 4篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1993年 | 4篇 |
1992年 | 4篇 |
1991年 | 8篇 |
1990年 | 8篇 |
1989年 | 5篇 |
1988年 | 9篇 |
1987年 | 5篇 |
1986年 | 5篇 |
1983年 | 5篇 |
1981年 | 6篇 |
1979年 | 5篇 |
1977年 | 4篇 |
1976年 | 5篇 |
1975年 | 7篇 |
1974年 | 8篇 |
1971年 | 4篇 |
1970年 | 3篇 |
1969年 | 7篇 |
1968年 | 3篇 |
1967年 | 6篇 |
1966年 | 3篇 |
1965年 | 3篇 |
排序方式: 共有939条查询结果,搜索用时 15 毫秒
21.
Marijana Popović Hadžija Marina Korolija Nikolina Jemin Iva Pavković Pajica Pavković Edita Pape Medvidović Mirko Hadžija 《Gene》2013
Genetic variants of IL-18 and IL-12B may be important in immunoregulatory abnormalities, observed in the patients with Type 1 diabetes mellitus (T1DM), that contribute to individual differences in response to a treatment. Therefore, we examined the significance of IL-18-137G/C, IL-18-607C/A, and IL-12B A/C polymorphisms in Croatians (187 patients, 236 controls), not only as factors that contribute to susceptibility to T1DM, but also as determinants of the clinical presentation of disease. 相似文献
22.
Bianca C. Pérez Iva Fernandes Nuno Mateus Cátia Teixeira Paula Gomes 《Bioorganic & medicinal chemistry letters》2013,23(24):6769-6772
Cinnamic acids and quinolines are known as useful scaffolds in the discovery of antitumor agents. Therefore, N-cinnamoylated analogues of chloroquine, recently reported as potent dual-action antimalarials, were evaluated against three different cancer cell lines: MKN-28, Caco-2, and MCF-7. All compounds display anti-proliferative activity in the micromolar range against the three cell lines tested, and most of them were more active than their parent drug, chloroquine, against all cell lines tested. Hence, N-cinnamoyl-chloroquine analogues are a good start towards development of affordable antitumor leads. 相似文献
23.
24.
Francesco V. Rao Alexander W. Schüttelkopf Helge C. Dorfmueller Andrew T. Ferenbach Iva Navratilova Daan M. F. van Aalten 《Open biology》2013,3(10)
The dynamic modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc) is an essential posttranslational modification present in higher eukaryotes. Removal of O-GlcNAc is catalysed by O-GlcNAcase, a multi-domain enzyme that has been reported to be bifunctional, possessing both glycoside hydrolase and histone acetyltransferase (AT) activity. Insights into the mechanism, protein substrate recognition and inhibition of the hydrolase domain of human OGA (hOGA) have been obtained via the use of the structures of bacterial homologues. However, the molecular basis of AT activity of OGA, which has only been reported in vitro, is not presently understood. Here, we describe the crystal structure of a putative acetyltransferase (OgpAT) that we identified in the genome of the marine bacterium Oceanicola granulosus, showing homology to the hOGA C-terminal AT domain (hOGA-AT). The structure of OgpAT in complex with acetyl coenzyme A (AcCoA) reveals that, by homology modelling, hOGA-AT adopts a variant AT fold with a unique loop creating a deep tunnel. The structures, together with mutagenesis and surface plasmon resonance data, reveal that while the bacterial OgpAT binds AcCoA, the hOGA-AT does not, as explained by the lack of key residues normally required to bind AcCoA. Thus, the C-terminal domain of hOGA is a catalytically incompetent ‘pseudo’-AT. 相似文献
25.
Yellow-related proteins (YRPs) present in sand fly saliva act as affinity binders of bioamines, and help the fly to complete a bloodmeal by scavenging the physiological signals of damaged cells. They are also the main antigens in sand fly saliva and their recombinant form is used as a marker of host exposure to sand flies. Moreover, several salivary proteins and plasmids coding these proteins induce strong immune response in hosts bitten by sand flies and are being used to design protecting vaccines against Leishmania parasites. In this study, thirty two 3D models of different yellow-related proteins from thirteen sand fly species of two genera were constructed based on the known protein structure from Lutzomyia longipalpis. We also studied evolutionary relationships among species based on protein sequences as well as sequence and structural variability of their ligand-binding site. All of these 33 sand fly YRPs shared a similar structure, including a unique tunnel that connects the ligand-binding site with the solvent by two independent paths. However, intraspecific modifications found among these proteins affects the charges of the entrances to the tunnel, the length of the tunnel and its hydrophobicity. We suggest that these structural and sequential differences influence the ligand-binding abilities of these proteins and provide sand flies with a greater number of YRP paralogs with more nuanced answers to bioamines. All these characteristics allow us to better evaluate these proteins with respect to their potential use as part of anti-Leishmania vaccines or as an antigen to measure host exposure to sand flies. 相似文献
26.
A high‐throughput capillary isoelectric focusing immunoassay for fingerprinting protein sialylation
下载免费PDF全文
![点击此处可从《Biotechnology progress》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Lam Raga Anggara Markely Lila Cheung Young Jun Choi Thomas Ryll Scott Estes Shashi Prajapati Iva Turyan Ruth Frenkel Zoran Sosic James Lambropoulos Lia Tescione Thomas Ryll Melissa Berman 《Biotechnology progress》2016,32(1):235-241
The serum half‐life, biological activity, and solubility of many recombinant glycoproteins depend on their sialylation. Monitoring glycoprotein sialylation during cell culture manufacturing is, therefore, critical to ensure product efficacy and safety. Here a high‐throughput method for semi‐quantitative fingerprinting of glycoprotein sialylation using capillary isoelectric focusing immunoassay on NanoPro (Protein Simple) platform was developed. The method was specific, sensitive, precise, and robust. It could analyze 2 μL of crude cell culture samples without protein purification, and could automatically analyze from 8 samples in 4 h to 96 samples in 14 h without analyst supervision. Furthermore, its capability to detect various changes in sialylation fingerprints during cell culture manufacturing process was indispensable to ensure process robustness and consistency. Moreover, the changes in the sialylation fingerprints analyzed by this method showed strong correlations with intact mass analysis using liquid chromatography and mass spectrometry. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 32:235–241, 2016 相似文献
27.
28.
29.
30.
Michelle A. Attner Wolfgang Keil Justin M. Benavidez Iva Greenwald 《Current biology : CB》2019,29(18):3094-3100.e4