全文获取类型
收费全文 | 298篇 |
免费 | 42篇 |
国内免费 | 1篇 |
出版年
2023年 | 3篇 |
2022年 | 4篇 |
2021年 | 10篇 |
2020年 | 6篇 |
2019年 | 7篇 |
2018年 | 10篇 |
2017年 | 5篇 |
2016年 | 10篇 |
2015年 | 23篇 |
2014年 | 21篇 |
2013年 | 25篇 |
2012年 | 20篇 |
2011年 | 22篇 |
2010年 | 20篇 |
2009年 | 13篇 |
2008年 | 19篇 |
2007年 | 19篇 |
2006年 | 14篇 |
2005年 | 15篇 |
2004年 | 13篇 |
2003年 | 9篇 |
2002年 | 10篇 |
2001年 | 4篇 |
2000年 | 5篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1993年 | 6篇 |
1992年 | 3篇 |
1990年 | 1篇 |
1987年 | 2篇 |
1985年 | 2篇 |
1982年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1970年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有341条查询结果,搜索用时 15 毫秒
1.
2.
L(-)-, and D(+)-enantiomers of 1-amino-2-phenylethylphosphonic acid (PheP), a phosphonic analogue of phenylalanine, inhibit the activity of L-phenylalanine ammonia-lyase (EC 4.3.1.5) of potato tuber tissue in vitro. The apparent type of inhibition depends on concentration of PheP; as the concentration of D-PheP is raised from 10(-5) M to 2.5 X 10(-3) M, the type of inhibition shifts from competitive through mixed and non-competitive to uncompetitive. L-PheP exerts either a competitive or mixed-type inhibition at low (10(-6)-10(-5) M) or moderate (5 X 10(-5)-2 X 10(-4) M) concentration. Ki for the concentration range of competitive inhibition were 6.5 X 10(-6) M, 5.3 X 10(-5)M and 1.6 X 10(-5) M for L-, D-, and D,L-PheP, respectively. These Ki values are valid for a relatively narrow range of L-Phe concentration (0.2-4 mM) as L-phenylalanine ammonia-lyase does not follow the Michaelis-Menten kinetics of the reaction. 相似文献
3.
4.
5.
In-vitro binding of labeled auxins to sedimentable particles was tested in subcellular fractions from homogenates of maize (Zea mays L.) coleoptiles. The material was fractionated by differential centrifugation or on sucrose density gradients. It was confirmed that the major saturable binding activity (site I) for 1-naphthyl[1-14C]acetic acid is associated with vesicles derived from the endoplasmatic reticulum. A second type of specific auxin binding (site II) could be distinguished by several criteria, e.g. by the low affinity towards phenylacetic acid. The particles carrying site II could be clearly separated from markers of the endoplasmatic reticulum, the plasmalemma, the mitochondria and the nuclei, while their density as well as sedimentation velocity correlated with particle-bound acid phosphatase, indicating a localization at the tonoplast. In contrast to site I, binding at site II was hardly affected by a supernatant factor and by sulfhydryl groups. However, the specificity pattern of site II towards auxins and auxin analogs was very similar to that of site I tested in the presence of supernatant factor. The existence of a third auxin receptor localized in plasma membrane-rich gradient fractions was indicated by a preferential in-vitro binding of 2,4-dichlorophenoxyacetic acid.Abbreviations 1-NAA
1-naphthyl acetic acid
- 2-NAA
2-naphthyl acetic acid
- IAA
3-indolyl acetic acid
- PAA
phenyl acetic acid
- 2,4-D
2,4-D-dichlorophenoxy acetic acid
- D-2,4-DP
dichlorophenoxy isopropionic acid
- NPA
1-N-naphthyl phthalamic acid
- ER
endoplasmatic reticulum
- SF
supernatant factor 相似文献
6.
Induction of NF-kappa B-like activity by platelet-derived growth factor in mouse fibroblasts. 总被引:3,自引:0,他引:3
下载免费PDF全文
![点击此处可从《Molecular biology of the cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Nuclear factor kappa B (NF-kappa B) modulates the expression of numerous genes via interaction with a specific DNA sequence termed the kappa B site. Its activity is modulated by a cytosolic inhibitor protein termed I kappa B, and its activation occurs in response to a variety of agents in a variety of cell types, most notably B and T lymphocytes. Data presented here show that an activity (designated complex I) that binds specifically to the kappa B site is induced in density-arrested Balb/c-3T3 mouse fibroblasts by platelet-derived growth factor (PDGF), a potent mitogen for these cells. Increased levels of complex I, as evaluated by electrophoretic mobility shift assays of nuclear extracts, were observed in cells treated for 1-4 h (but not 15 min) with the BB isoform of PDGF. 12-O-tetradecanoylphorbol 13-acetate (TPA) and the AA isoform of PDGF also stimulated this response and both isoforms, but not TPA, were effective in cells depleted of protein kinase C. Complex I most likely is authentic NF-kappa B, a p50-p65 heterodimer, or a closely related factor because it exhibited properties characteristic of those previously described for NF-kappa B including inducibility by deoxycholate and cycloheximide and sensitivity to I kappa B. A second kappa B binding activity (complex II), which apparently contained p50 homodimers, displayed limited induction by PDGF, whereas a third complex (complex III) migrated faster than but behaved similarly to complex I. These studies suggest that NF-kappa B or an NF-kappa B-like factor may participate in the expression of PDGF-inducible genes. 相似文献
7.
8.
Mohammad-Reza Ghovanloo Koushik Choudhury Tagore S. Bandaru Mohamed A. Fouda Kaveh Rayani Radda Rusinova Tejas Phaterpekar Karen Nelkenbrecher Abeline R. Watkins Damon Poburko Jenifer Thewalt Olaf S. Andersen Lucie Delemotte Samuel J. Goodchild Peter C. Ruben 《The Journal of general physiology》2021,153(5)
Cannabidiol (CBD) is the primary nonpsychotropic phytocannabinoid found in Cannabis sativa, which has been proposed to be therapeutic against many conditions, including muscle spasms. Among its putative targets are voltage-gated sodium channels (Navs), which have been implicated in many conditions. We investigated the effects of CBD on Nav1.4, the skeletal muscle Nav subtype. We explored direct effects, involving physical block of the Nav pore, as well as indirect effects, involving modulation of membrane elasticity that contributes to Nav inhibition. MD simulations revealed CBD’s localization inside the membrane and effects on bilayer properties. Nuclear magnetic resonance (NMR) confirmed these results, showing CBD localizing below membrane headgroups. To determine the functional implications of these findings, we used a gramicidin-based fluorescence assay to show that CBD alters membrane elasticity or thickness, which could alter Nav function through bilayer-mediated regulation. Site-directed mutagenesis in the vicinity of the Nav1.4 pore revealed that removing the local anesthetic binding site with F1586A reduces the block of INa by CBD. Altering the fenestrations in the bilayer-spanning domain with Nav1.4-WWWW blocked CBD access from the membrane into the Nav1.4 pore (as judged by MD). The stabilization of inactivation, however, persisted in WWWW, which we ascribe to CBD-induced changes in membrane elasticity. To investigate the potential therapeutic value of CBD against Nav1.4 channelopathies, we used a pathogenic Nav1.4 variant, P1158S, which causes myotonia and periodic paralysis. CBD reduces excitability in both wild-type and the P1158S variant. Our in vitro and in silico results suggest that CBD may have therapeutic value against Nav1.4 hyperexcitability. 相似文献
9.
Zaida Araujo Francesca Giampietro María de los Angeles Bochichio Andrea Palacios Jenifer Dinis Jaime Isern Jacobus Henry de Waard Elsa Rada Rafael Borges Carlos Fernández de Larrea Angel Villasmil Magnolia Vanegas Jose Antonio Enciso-Moreno Manuel Alfonso Patarroyo 《Memórias do Instituto Oswaldo Cruz》2013,108(2):131-139
The goal of this study was to demonstrate the usefulness of an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of pulmonary tuberculosis (PTB) and extrapulmonary TB (EPTB). This assay used 20 amino acid-long, non-overlapped synthetic peptides that spanned the complete Mycobacterium tuberculosis ESAT-6 and Ag85A sequences. The validation cohort consisted of 1,102 individuals who were grouped into the following five diagnostic groups: 455 patients with PTB, 60 patients with EPTB, 40 individuals with non-EPTB, 33 individuals with leprosy and 514 healthy controls. For the PTB group, two ESAT-6 peptides (12033 and 12034) had the highest sensitivity levels of 96.9% and 96.2%, respectively, and an Ag85A-peptide (29878) was the most specific (97.4%) in the PTB groups. For the EPTB group, two Ag85A peptides (11005 and 11006) were observed to have a sensitivity of 98.3% and an Ag85A-peptide (29878) was also the most specific (96.4%). When combinations of peptides were used, such as 12033 and 12034 or 11005 and 11006, 99.5% and 100% sensitivities in the PTB and EPTB groups were observed, respectively. In conclusion, for a cohort that consists entirely of individuals from Venezuela, a multi-antigen immunoassay using highly sensitive ESAT-6 and Ag85A peptides alone and in combination could be used to more rapidly diagnose PTB and EPTB infection. 相似文献
10.
Jenifer L. Smith Kassandra I. Rossiter Christopher M. Semko Ying-Zi Xu David A. Quincy Jacek Jagodzinski Michael S. Dappen Andrei W. Konradi Christopher Vandevert Caroline Garrido Wenxian Mao F. Bong San Pablo Brian Wipke Lilibeth Dofiles Angie Wadsworth Eric Peterson Carlos Lorenzana Stellanie Simmonds Ted A. Yednock 《Bioorganic & medicinal chemistry letters》2013,23(14):4117-4119
Mitsunobu reactions were employed to link t-butyl esters of α4 integrin inhibitors at each of the termini of a three-arm, 40 kDa, branched PEG. Cleavage of the t-butyl esters using HCO2H provided easily isolated PEG derivatives, which are potent α4 integrin inhibitors, and which achieve sustained levels and bioactivity in vivo, following subcutaneous administration to rats. 相似文献