全文获取类型
收费全文 | 144篇 |
免费 | 15篇 |
出版年
2022年 | 2篇 |
2021年 | 1篇 |
2020年 | 2篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2017年 | 4篇 |
2016年 | 9篇 |
2015年 | 9篇 |
2014年 | 10篇 |
2013年 | 6篇 |
2012年 | 12篇 |
2011年 | 14篇 |
2010年 | 12篇 |
2009年 | 9篇 |
2008年 | 9篇 |
2007年 | 8篇 |
2006年 | 6篇 |
2005年 | 7篇 |
2004年 | 4篇 |
2003年 | 3篇 |
2002年 | 3篇 |
2001年 | 4篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 2篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1973年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有159条查询结果,搜索用时 15 毫秒
1.
Translational coupling in Escherichia coli of a heterologous Bacillus subtilis-Escherichia coli gene fusion. 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Journal of bacteriology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The efficient expression in Escherichia coli of the Tn9-derived chloramphenicol acetyltransferase (EC 2.3.1.28) gene fused distal to the promoter and N terminus of the Bacillus subtilis aprA gene was dependent on the initiation of translation from the ribosome-binding site in the aprA gene. 相似文献
2.
3.
Pedro M. D. Moreno Sylvain Geny Y. Vladimir Pabon Helen Bergquist Eman M. Zaghloul Cristina S. J. Rocha Iulian I. Oprea Burcu Bestas Samir EL Andaloussi Per T. J?rgensen Erik B. Pedersen Karin E. Lundin Rula Zain Jesper Wengel C. I. Edvard Smith 《Nucleic acids research》2013,41(5):3257-3273
In spite of the many developments in synthetic oligonucleotide (ON) chemistry and design, invasion into double-stranded DNA (DSI) under physiological salt and pH conditions remains a challenge. In this work, we provide a new ON tool based on locked nucleic acids (LNAs), designed for strand invasion into duplex DNA (DSI). We thus report on the development of a clamp type of LNA ON—bisLNA—with capacity to bind and invade into supercoiled double-stranded DNA. The bisLNA links a triplex-forming, Hoogsteen-binding, targeting arm with a strand-invading Watson–Crick binding arm. Optimization was carried out by varying the number and location of LNA nucleotides and the length of the triplex-forming versus strand-invading arms. Single-strand regions in target duplex DNA were mapped using chemical probing. By combining design and increase in LNA content, it was possible to achieve a 100-fold increase in potency with 30% DSI at 450 nM using a bisLNA to plasmid ratio of only 21:1. Although this first conceptual report does not address the utility of bisLNA for the targeting of DNA in a chromosomal context, it shows bisLNA as a promising candidate for interfering also with cellular genes. 相似文献
4.
Mohamed Zaghloul Christoph Reisch Peter Poschlod 《Plant Systematics and Evolution》2013,299(10):1819-1828
The contribution of soil seed bank of a desert endemic plant species in maintaining genetic diversity has been addressed in this paper through investigating the differences in genetic diversity and structure (using AFLP markers) between plants grown from soil seed bank and standing crop plants within and among five populations of H. sinaicum growing at St. Katherine Protectorate, southern Sinai, Egypt. Standard genetic diversity measures showed that the molecular variation within and among populations was highly significantly different between standing crop and soil seed bank. While soil seed bank had lower genetic diversity than standing crop populations, pooling soil seed bank with standing crop samples resulted in higher diversity. The results revealed also that soil seed bank had lower differentiation (7 %) than among populations of the standing crop (18 %). Results of neighbor-joining, Bayesian clustering and principal coordinate analysis showed that soil seed banks had a separate gene pool different from standing crop. The study came to the conclusion that the genetic variation of the soil seed bank contributes significantly to the genetic variation of the species. This also stresses the importance of elucidating the genetic diversity and structure of the soil seed bank for any sound and long-term conservation efforts for desert species. These have been growing in small-size populations for a long time that any estimates gained only from aboveground sampling of populations may be ambiguous. 相似文献
5.
Siegel DH Ashton GH Penagos HG Lee JV Feiler HS Wilhelmsen KC South AP Smith FJ Prescott AR Wessagowit V Oyama N Akiyama M Al Aboud D Al Aboud K Al Githami A Al Hawsawi K Al Ismaily A Al-Suwaid R Atherton DJ Caputo R Fine JD Frieden IJ Fuchs E Haber RM Harada T Kitajima Y Mallory SB Ogawa H Sahin S Shimizu H Suga Y Tadini G Tsuchiya K Wiebe CB Wojnarowska F Zaghloul AB Hamada T Mallipeddi R Eady RA McLean WH McGrath JA Epstein EH 《American journal of human genetics》2003,73(1):174-187
Kindler syndrome is an autosomal recessive disorder characterized by neonatal blistering, sun sensitivity, atrophy, abnormal pigmentation, and fragility of the skin. Linkage and homozygosity analysis in an isolated Panamanian cohort and in additional inbred families mapped the gene to 20p12.3. Loss-of-function mutations were identified in the FLJ20116 gene (renamed “KIND1” [encoding kindlin-1]). Kindlin-1 is a human homolog of the Caenorhabditis elegans protein UNC-112, a membrane-associated structural/signaling protein that has been implicated in linking the actin cytoskeleton to the extracellular matrix (ECM). Thus, Kindler syndrome is, to our knowledge, the first skin fragility disorder caused by a defect in actin-ECM linkage, rather than keratin-ECM linkage. 相似文献
6.
Jessica AB van Nies Rute B Marques Stella Trompet Zuzana de Jong Fina AS Kurreeman Rene EM Toes J Wouter Jukema Tom WJ Huizinga Annette HM van der Helm-van Mil 《Arthritis research & therapy》2010,12(2):R38
Introduction
Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients. 相似文献7.
Intervention with mesenchymal stem cells (MSCs) represents a promising therapeutic tool in treatment-refractory autoimmune
diseases. A new report by Schurgers and colleagues in a previous issue of Arthritis Research & Therapy sheds novel mechanistic insight into the pathways employed by MSCs to suppress T-cell proliferation in vitro, but, at the same time, indicates that MSCs do not influence T-cell reactivity and the disease course in an in vivo arthritis model. Such discrepancies between the in vitro and in vivo effects of potent cellular immune modulators should spark further research and should be interpreted as a sign of caution
for the in vitro design of MSC-derived interventions in the setting of human autoimmune diseases. 相似文献
8.
Kaiser A Hammels I Gottwald A Nassar M Zaghloul MS Motaal BA Hauber J Hoerauf A 《Bioorganic & medicinal chemistry》2007,15(18):6200-6207
9.
Bahareh Honarparvar Sachin A Pawar Cláudio Nahum Alves Jer?nimo Lameira Glenn EM Maguire José Rogério A Silva Thavendran Govender Hendrik G Kruger 《Journal of biomedical science》2015,22(1)
Background
Novel pentacycloundecane (PCU)-lactone-CO-EAIS peptide inhibitors were designed, synthesized, and evaluated against wild-type C-South African (C-SA) HIV-1 protease. Three compounds are reported herein, two of which displayed IC50 values of less than 1.00 μM. A comparative MM-PB(GB)SA binding free energy of solvation values of PCU-lactam and lactone models and their enantiomers as well as the PCU-lactam-NH-EAIS and lactone-CO-EAIS peptide inhibitors and their corresponding diastereomers complexed with South African HIV protease (C-SA) was performed. This will enable us to rationalize the considerable difference between inhibitory concentration (IC50) of PCU-lactam-NH-EAIS and PCU-lactone-CO-EAIS peptides.Results
The PCU-lactam model exhibited more negative calculated binding free energies of solvation than the PCU-lactone model. The same trend was observed for the PCU-peptide inhibitors, which correspond to the experimental activities for the PCU-lactam-NH-EAIS peptide (IC50 = 0.076 μM) and the PCU-lactone-CO-EAIS peptide inhibitors (IC50 = 0.850 μM). Furthermore, a density functional theory (DFT) study on the natural atomic charges of the nitrogen and oxygen atoms of the three PCU-lactam, PCU-lactim and PCU-lactone models were performed using natural bond orbital (NBO) analysis. Electrostatic potential maps were also used to visualize the electron density around electron-rich regions. The asymmetry parameter (η) and quadrupole coupling constant (χ) values of the nitrogen and oxygen nuclei of the model compounds were calculated at the same level of theory. Electronic molecular properties including polarizability and electric dipole moments were also calculated and compared. The Gibbs theoretical free solvation energies of solvation (∆Gsolv) were also considered.Conclusions
A general trend is observed that the lactam species appears to have a larger negative charge distribution around the heteroatoms, larger quadrupole constant, dipole moment and better solvation energy, in comparison to the PCU-lactone model. It can be argued that these characteristics will ensure better eletronic interaction between the lactam and the receptor, corresponding to the observed HIV protease activities in terms of experimental IC50 data.Electronic supplementary material
The online version of this article (doi:10.1186/s12929-015-0115-5) contains supplementary material, which is available to authorized users. 相似文献10.
Nadine Kraemer Ethiraj Ravindran Sami Zaqout Gerda Neubert Detlev Schindler Olaf Ninnemann Ralph Gr?f Andrea EM Seiler Angela M Kaindl 《Cell cycle (Georgetown, Tex.)》2015,14(13):2044-2057
Biallelic mutations in the gene encoding centrosomal CDK5RAP2 lead to autosomal recessive primary microcephaly (MCPH), a disorder characterized by pronounced reduction in volume of otherwise architectonical normal brains and intellectual deficit. The current model for the microcephaly phenotype in MCPH invokes a premature shift from symmetric to asymmetric neural progenitor-cell divisions with a subsequent depletion of the progenitor pool. The isolated neural phenotype, despite the ubiquitous expression of CDK5RAP2, and reports of progressive microcephaly in individual MCPH cases prompted us to investigate neural and non-neural differentiation of Cdk5rap2-depleted and control murine embryonic stem cells (mESC). We demonstrate an accumulating proliferation defect of neurally differentiating Cdk5rap2-depleted mESC and cell death of proliferative and early postmitotic cells. A similar effect does not occur in non-neural differentiation into beating cardiomyocytes, which is in line with the lack of non-central nervous system features in MCPH patients. Our data suggest that MCPH is not only caused by premature differentiation of progenitors, but also by reduced propagation and survival of neural progenitors. 相似文献