全文获取类型
收费全文 | 341篇 |
免费 | 16篇 |
专业分类
357篇 |
出版年
2023年 | 3篇 |
2022年 | 7篇 |
2021年 | 16篇 |
2020年 | 8篇 |
2019年 | 16篇 |
2018年 | 14篇 |
2017年 | 10篇 |
2016年 | 18篇 |
2015年 | 24篇 |
2014年 | 21篇 |
2013年 | 21篇 |
2012年 | 35篇 |
2011年 | 35篇 |
2010年 | 19篇 |
2009年 | 10篇 |
2008年 | 14篇 |
2007年 | 26篇 |
2006年 | 14篇 |
2005年 | 15篇 |
2004年 | 4篇 |
2003年 | 7篇 |
2002年 | 5篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 1篇 |
1997年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1985年 | 1篇 |
1974年 | 1篇 |
1940年 | 1篇 |
排序方式: 共有357条查询结果,搜索用时 0 毫秒
81.
82.
83.
84.
A small-scale, homogeneous, rapid sensing system for phenothiazines and tricyclic antidepressants (TCAs) has been developed by employing fluorescently labeled mutant calmodulin (CaM) as the recognition element. A calmodulin mutant containing a unique cysteine residue at position 109 on the protein was expressed in Escherichia coli. Following purification, the environment-sensitive, thiol-specific fluorophores N-[2-(1-maleimidyl)ethyl]-7-(diethylamino)coumarin-3-carboxamide (MDCC), 6-acryloyl-2-dimethylaminonaphthalene (acrylodan), and 4-[N-(2-(iodoacetoxy)ethyl)-N-methylamino]-7-nitrobenz-2-oxa-1,3-diazole (IANBD ester) were coupled to the C109 site of the mutant protein. The response of labeled CaM in the presence of calcium to increasing concentrations of chlorpromazine hydrochloride (CPZ), as well as other phenothiazines and structurally related antipsychotics and antidepressants, was investigated. Fluorescence measurements were performed on benchtop and microtiter plate fluorometers. The responses were characterized as a change in the signal intensity of the labeled protein upon ligand binding, and the stability of the system was monitored over a nine-month period. The assay showed specificity for the phenothiazine and TCA classes of drugs, with limits of detection in the micromolar range. Selectivity studies indicated negligible response of the biosensing system to structurally unrelated compounds. This work represents a proof-of-concept assay for rapid, homogeneous detection of drugs employing binding proteins as the biorecognition element. 相似文献
85.
86.
Wilhelm Ching Emre Koyuncu Sonia Singh Christina Arbelo-Roman Barbara Hartl Elisabeth Kremmer Thomas Speiseder Chris Meier Thomas Dobner 《PLoS pathogens》2013,9(3)
Adenoviral replication depends on viral as well as cellular proteins. However, little is known about cellular proteins promoting adenoviral replication. In our screens to identify such proteins, we discovered a cellular component of the ubiquitin proteasome pathway interacting with the central regulator of adenoviral replication. Our binding assays mapped a specific interaction between the N-terminal domains of both viral E1B-55K and USP7, a deubiquitinating enzyme. RNA interference-mediated downregulation of USP7 severely reduced E1B-55K protein levels, but more importantly negatively affected adenoviral replication. We also succeeded in resynthesizing an inhibitor of USP7, which like the knockdown background reduced adenoviral replication. Further assays revealed that not only adenoviral growth, but also adenoviral oncogene-driven cellular transformation relies on the functions of USP7. Our data provide insights into an intricate mechanistic pathway usurped by an adenovirus to promote its replication and oncogenic functions, and at the same time open up possibilities for new antiviral strategies. 相似文献
87.
SUMMARY: We present our protein-protein interaction (PPI) network visualization system RobinViz (reliability-oriented bioinformatic networks visualization). Clustering the PPI network based on gene ontology (GO) annotations or biclustered gene expression data, providing a clustered visualization model based on a central/peripheral duality, computing layouts with algorithms specialized for interaction reliabilities represented as weights, completely automated data acquisition, processing are notable features of the system. AVAILABILITY: RobinViz is a free, open-source software protected under GPL. It is written in C++ and Python, and consists of almost 30 000 lines of code, excluding the employed libraries. Source code, user manual and other Supplementary Material are available for download at http://code.google.com/p/robinviz/. 相似文献
88.
This study used karyological techniques to determine the chromosome numbers and morphology of eight species of Onobrychis L. (O. caput-galli (L.) Lam, O. aequidentata (Sibth. & Sm.) d’ Urv, O. fallax Freyn & Sint. var. fallax, O. lasiostachya Boiss, O. viciifolia Scop., O. oxyodonta Boiss. subsp. armena (Bois. & Huet) Aktoklu, O. hypargyrea Boiss. and O. cappadocica Boiss.). The results of this study determined the chromosome numbers of O. cappadocica as 2n = 16; O. viciifolia as 2n = 28 and the other species as 2n = 14 The karyotypes of species consisted of median-centromeric (m) or submedian-centromeric (sm) chromosomes. However, O. oxyodonta Boiss. subsp. armena (Bois. & Huet) Aktoklu was found to have only the median-centromeric (m) chromosomes. According to the results of the present
study, of the eight Onobrychis taxa, only O. hypargyrea has a pair of satellite chromosomes (sat-chromosome). Furthermore, this study detected karyotype asymmetry. 相似文献
89.
Guven Gamze Bilgic Basar Samanci Bedia Gurvit Hakan Hanagasi Hasmet Donmez Cagla Aslan Rukiye Lohmann Ebba Erginel-Unaltuna Nihan 《Molecular biology reports》2020,47(8):5903-5909
Molecular Biology Reports - ‘Triggering receptor expressed on myeloid cells 2’ (TREM2) gene is involved in Alzheimer’s disease (AD) and TREM2 mRNA expression is known to be... 相似文献
90.
The kinase VRK1 has been implicated in mitotic and meiotic progression in invertebrate species, but whether it mediates these events during mammalian gametogenesis is not completely understood. Previous work has demonstrated a role for mammalian VRK1 in proliferation of male spermatogonia, yet whether VRK1 plays a role in meiotic progression, as seen in Drosophila, has not been determined. Here, we have established a mouse strain bearing a gene trap insertion in the VRK1 locus that disrupts Vrk1 expression. In addition to the male proliferation defects, we find that reduction of VRK1 activity causes a delay in meiotic progression during oogenesis, results in the presence of lagging chromosomes during formation of the metaphase plate, and ultimately leads to the failure of oocytes to be fertilized. The activity of at least one phosphorylation substrate of VRK1, p53, is not required for these defects. These results are consistent with previously defined functions of VRK1 in meiotic progression in Drosophila oogenesis, and indicate a conserved role for VRK1 in coordinating proper chromosomal configuration in female meiosis. 相似文献