全文获取类型
收费全文 | 92篇 |
免费 | 4篇 |
国内免费 | 1篇 |
出版年
2021年 | 2篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 2篇 |
2016年 | 2篇 |
2015年 | 4篇 |
2014年 | 3篇 |
2013年 | 9篇 |
2012年 | 5篇 |
2011年 | 7篇 |
2009年 | 1篇 |
2007年 | 5篇 |
2006年 | 7篇 |
2005年 | 2篇 |
2004年 | 2篇 |
2003年 | 1篇 |
2002年 | 3篇 |
2001年 | 3篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1997年 | 1篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 6篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有97条查询结果,搜索用时 15 毫秒
21.
The structural basis of the TIM10 chaperone assembly 总被引:5,自引:0,他引:5
Lu H Golovanov AP Alcock F Grossmann JG Allen S Lian LY Tokatlidis K 《The Journal of biological chemistry》2004,279(18):18959-18966
Tim9 and Tim10 are essential components of the "small Tim" family of proteins that facilitate insertion of polytopic proteins at the inner mitochondrial membrane. The small Tims are themselves imported from the cytosol and are organized in specific translocation assemblies in the intermembrane space. Their conformational properties and how these influence the mechanism of assembly remain poorly understood. Moreover, the three-dimensional structure of the TIM10 complex is unknown. We have characterized the structural properties of these proteins in their free and assembled states using NMR, circular dichroism, and small angle x-ray scattering. We show that the free proteins are largely unfolded in their reduced assembly-incompetent state and molten globules in their oxidized assembly-competent state. Tim10 appears less structured than Tim9 in their respective free oxidized forms and undergoes a larger structural change than Tim9 upon complexation. The NMR data here demonstrates unequivocally that only the oxidized states of the Tim9 and Tim10 proteins are capable of forming a complex. Zinc binding stabilizes the reduced state against proteolysis without significantly affecting the secondary structure. Solution x-ray scattering was used to obtain a molecular envelope for the subunits individually and for their fully functional TIM10 complex. Ab initio shape reconstructions based on the scattering data has allowed us to obtain the first low resolution three-dimensional structure of the TIM10 complex. This is a novel structure that displays extensive surface hydrophobicity. The structure also provides an explanation for the escorting function of this non-ATP-powered chaperone particle. 相似文献
22.
Fedoroff OY Townson SA Golovanov AP Baron M Avis JM 《The Journal of biological chemistry》2004,279(33):34991-35000
WW domains mediate protein recognition, usually though binding to proline-rich sequences. In many proteins, WW domains occur in tandem arrays. Whether or how individual domains within such arrays cooperate to recognize biological partners is, as yet, poorly characterized. An important question is whether functional diversity of different WW domain proteins is reflected in the structural organization and ligand interaction mechanisms of their multiple domains. We have determined the solution structure and dynamics of a pair of WW domains (WW3-4) from a Drosophila Nedd4 family protein called Suppressor of deltex (Su(dx)), a regulator of Notch receptor signaling. We find that the binding of a type 1 PPPY ligand to WW3 stabilizes the structure with effects propagating to the WW4 domain, a domain that is not active for ligand binding. Both WW domains adopt the characteristic triple-stranded beta-sheet structure, and significantly, this is the first example of a WW domain structure to include a domain (WW4) lacking the second conserved Trp (replaced by Phe). The domains are connected by a flexible linker, which allows a hinge-like motion of domains that may be important for the recognition of functionally relevant targets. Our results contrast markedly with those of the only previously determined three-dimensional structure of tandem WW domains, that of the rigidly oriented WW domain pair from the RNA-splicing factor Prp40. Our data illustrate that arrays of WW domains can exhibit a variety of higher order structures and ligand interaction mechanisms. 相似文献
23.
24.
Courtney D. Fitzhugh Matthew M. Hsieh Darlene Allen Wynona A. Coles Cassie Seamon Michael Ring Xiongce Zhao Caterina P. Minniti Griffin P. Rodgers Alan N. Schechter John F. Tisdale James G. Taylor VI 《PloS one》2015,10(11)
Background
Adults with sickle cell anemia (HbSS) are inconsistently treated with hydroxyurea.Objectives
We retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010.Methods
An electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose. This study is registered with ClinicalTrials.gov, number NCT00011648.Results
Three hundred eighty-three adults with homozygous sickle cell disease were analyzed with 59 deaths during study follow-up. Cox regression analysis revealed deceased subjects had more hepatic dysfunction (elevated alkaline phosphatase, Hazard Ratio = 1.005, 95% CI 1.003–1.006, p<0.0.0001), kidney dysfunction (elevated creatinine, Hazard Ratio = 1.13, 95% CI 1.00–1.27, p = 0.043), and cardiopulmonary dysfunction (elevated tricuspid jet velocity on echocardiogram, Hazard Ratio = 2.22, 1.23–4.02, p = 0.0082). Sixty-six percent of subjects were treated with hydroxyurea, although only 66% of those received a dose within the recommended therapeutic range. Hydroxyurea use was associated with improved survival (Hazard Ratio = 0.58, 95% CI 0.34–0.97, p = 0.040). This effect was most pronounced in those taking the recommended dose of 15–35 mg/kg/day (Hazard Ratio 0.36, 95% CI 0.17–0.73, p = 0.0050). Hydroxyurea use was not associated with changes in organ function over time. Further, subjects with higher fetal hemoglobin responses to hydroxyurea were more likely to survive (p = 0.0004). While alkaline phosphatase was lowest in patients with the best fetal hemoglobin response (95.4 versus 123.6, p = 0.0065 and 96.1 versus 113.6U/L, p = 0.041 at first and last visits, respectively), other markers of organ damage were not consistently improved over time in patients with the highest fetal hemoglobin levels.Conclusions
Our data suggest that adults should be treated with the maximum tolerated hydroxyurea dose, ideally before organ damage occurs. Prospective studies are indicated to validate these findings. 相似文献25.
OL Garibay-Cerdenares VI Hernández-Ramírez JC Osorio-Trujillo D Gallardo-Rincón P Talamás-Rohana 《Cell Adhesion & Migration》2015,9(5):394-405
Haptoglobin (Hp) is an acute-phase protein that is produced by the liver to capture the iron that is present in the blood circulation, thus avoiding its accumulation in the blood. Moreover, Hp has been detected in a wide variety of tissues, in which it performs various functions. In addition, this protein is considered a potential biomarker in many diseases, such as cancer, including ovarian carcinoma; however, its participation in the cancerous processes has not yet been determined. The objective of this work was to demonstrate the expression of Hp and its receptor CCR2 in the ovarian cancer cells and its possible involvement in the process of cell migration through changes in the rearrangement of the actin cytoskeleton using western blot and wound-healing assays and confirming by confocal microscopy. Ovarian cancer cells express both Hp and its receptor CCR2 but only after exposure to ascitic fluid, inducing moderated cell migration. However, when the cells are exposed to exogenous Hp, the expression of CCR2 is induced together with drastic changes in the actin cytoskeleton rearrangement. At the same time, Hp induced cell migration in a much more efficient manner than did ascitic fluid. These effects were blocked when the CCR2 synthetic antagonist RS102895 was used to pretreat the cells. These results suggest that Hp-induced changes in the cell morphology, actin cytoskeleton structure, and migration ability of tumor cells, is possibly “preparing” these cells for the potential induction of the metastatic phenotype. 相似文献
26.
Uybach Vo Kevin J. Embrey Alexander L. Breeze Alexander P. Golovanov 《Biomolecular NMR assignments》2013,7(2):215-219
K-Ras, a member of the Ras family of small GTPases, is involved in cell growth, proliferation, differentiation and apoptosis and is frequently mutated in cancer. The activity of Ras is mediated by the inter-conversion between GTP- and GDP- bound states. This conversion is regulated by binding of effector proteins such as guanine nucleotide exchange factors and GTPase activating proteins. Previously, NMR signals from these effector-binding regions of Ras often remained unassigned and largely unobservable due to conformational exchange and polysterism inherent to this protein. In this paper, we report the complete backbone and Cβ, as well as partial Hα, Hβ and Cγ, NMR assignment for human K-Ras (residues 1–166) in the GDP-bound form at a physiological pH of 7.4. These data thereby make possible detailed monitoring of the functional cycle of Ras and its interactions with nucleotides and effector proteins through the observation of fingerprint signals from all the functionally important regions of the protein. 相似文献
27.
28.
29.
30.
Results from the 1993–2004 genetic monitoring of pink salmon populations reproducing in the rivers of Tauy Bay on the Sea
of Okhotsk are analyzed. A statistically significant heterogeneity of samples as determined by gene frequencies is found only
in the pink salmon generations of even years. The genetic differentiation of samples from even years (GST = 1.39 ± 0.41) is higher than that of odd years (GST = 0.740.09). The pattern for the indicator of genetic variability (heterozygosity) is exactly the opposite (0.076 ± 0.02564
vs. 0.8760 ± 0.01950). Consequently, the lower-heterozygosity samples of lines from even years are on average more genetically
distinct than the analogous indicator for odd years. In addition, the interpopulation ratio in the general value of genetic
diversity is almost always smaller than both the intraannual and interannual ratios, leading to a low level of interpopulation
genetic differences. Cluster analysis reveals that most 2001–2004 samples are grouped separately from samples collected prior
to 2000. In our opinion, the reason for this could be the turnover of a numerically dominant generation of northern Sea of
Okhtosk pink salmon and the change in gene frequencies accompanying it. 相似文献