全文获取类型
收费全文 | 2166篇 |
免费 | 215篇 |
出版年
2023年 | 5篇 |
2022年 | 8篇 |
2021年 | 32篇 |
2020年 | 25篇 |
2019年 | 59篇 |
2018年 | 56篇 |
2017年 | 54篇 |
2016年 | 69篇 |
2015年 | 86篇 |
2014年 | 100篇 |
2013年 | 130篇 |
2012年 | 159篇 |
2011年 | 153篇 |
2010年 | 82篇 |
2009年 | 93篇 |
2008年 | 111篇 |
2007年 | 111篇 |
2006年 | 99篇 |
2005年 | 88篇 |
2004年 | 80篇 |
2003年 | 66篇 |
2002年 | 72篇 |
2001年 | 67篇 |
2000年 | 63篇 |
1999年 | 62篇 |
1998年 | 32篇 |
1997年 | 22篇 |
1996年 | 30篇 |
1995年 | 22篇 |
1994年 | 14篇 |
1993年 | 14篇 |
1992年 | 28篇 |
1991年 | 40篇 |
1990年 | 36篇 |
1989年 | 22篇 |
1988年 | 26篇 |
1987年 | 23篇 |
1986年 | 23篇 |
1985年 | 24篇 |
1984年 | 8篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 6篇 |
1978年 | 9篇 |
1977年 | 7篇 |
1974年 | 12篇 |
1973年 | 6篇 |
1972年 | 5篇 |
1969年 | 4篇 |
排序方式: 共有2381条查询结果,搜索用时 15 毫秒
1.
Side chain flexibility and coupling between the S4‐S5 linker and the TRP domain in thermo‐sensitive TRP channels: Insights from protein modeling 下载免费PDF全文
The transient receptor potential (TRP) superfamily is subdivided into several subfamilies on the basis of sequence similarity, which is highly heterogeneous but shows a molecular architecture that resembles the one present in members of the Kv channel superfamily. Because of this diversity, they produce a large variety of channels with different gating and permeability properties. Elucidation of these particular features necessarily requires comparative studies based on structural and functional data. The present study aims to compilate, analyze, and determine, in a coherent way, the relationship between intrinsic side‐chain flexibility and the allosteric coupling in members of the TRPV, TRPM, and TRPC families. Based on the recently determined structures of TRPV1 and TRPV2, we have generated protein models for single subunits of TRPV5, TRPM8, and TRPC5 channels. With these models, we focused our attention on the apparently crucial role of the GP dipeptide at the center of the S4‐S5 linker and discussed its role in the interaction with the TRP domain, specifically with the highly‐conserved Trp during this coupling. Our analysis suggests an important role of the S4‐S5L flexibility in the thermosensitivity, where heat‐activated channels possess rigid S4‐S5 linkers, whereas cold‐activated channels have flexible ones. Finally, we also present evidence of the key interaction between the conserved Trp residue of the TRP box and of several residues in the S4‐S5L, importantly the central Pro. Proteins 2017; 85:630–646. © 2016 Wiley Periodicals, Inc. 相似文献
2.
Marielle Ernst Javier M. Romero Jan-Hendrik Buhk Bastian Cheng Jochen Herrmann Jens Fiehler Michael Groth 《PloS one》2015,10(10)
Purpose
The hyperdense basilar artery sign (HBAS) is an indicator of vessel occlusion on non contrast-enhanced computer tomography (NECT) in acute stroke patients. Since basilar artery occlusion (BAO) is associated with a high mortality and morbidity, its early detection is of great clinical value. We sought to analyze the influence of density measurement as well as a normalized ratio of Hounsfield unit/hematocrit (HU/Hct) ratio on the detection of BAO on NECT in patients with suspected BAO.Materials and Methods
102 patients with clinically suspected BAO were examined with NECT followed immediately by Multidetector computed tomography Angiography. Two observers independently analyzed the images regarding the presence or absence of HBAS on NECT and performed HU measurements in the basilar artery. Receiver operating characteristic curve analysis was performed to determine the optimal density threshold for BAO using attenuation measurements or HU/Hct ratio.Results
Sensitivity of visual detection of the HBAS on NECT was relatively low 81% (95%-CI, 54–95%) while specificity was high 91% (95%-CI, 82–96%). The highest sensitivity was achieved by the combination of visual assessment and additional quantitative attenuation measurements applying a cut-off value of 46.5 HU with 94% sensitivity and 81% specificity for BAO. A HU/Hct ratio >1.32 revealed sensitivity of 88% (95%-CI, 60–98%) and specificity of 84% (95%-CI, 74–90%).Conclusion
In patients with clinically suspected acute BAO the combination of visual assessment and additional attenuation measurement with a cut-off value of 46.5 HU is a reliable approach with high sensitivity in the detection of BAO on NECT. 相似文献3.
Gabrielli Matías Romero Damián G. Martini Claudia N. Raiger Iustman Laura Judith Vila María del C. 《Molecular and cellular biochemistry》2018,448(1-2):299-309
Molecular and Cellular Biochemistry - We investigated for the first time the expression of melanoma cell adhesion molecule (MCAM) and its involvement in the differentiation of 3T3-L1 fibroblasts to... 相似文献
4.
Journal of Ichthyology - Allometric power equations are generated using otolith length and width in order to estimate the total length of five demersal species inhabiting the San Matias Gulf, the... 相似文献
5.
Signaling in the plant cytosol: cysteine or sulfide? 总被引:1,自引:0,他引:1
Cecilia Gotor Ana M. Laureano-Marín Inmaculada Moreno Ángeles Aroca Irene García Luis C. Romero 《Amino acids》2015,47(10):2155-2164
Cysteine (Cys) is the first organic compound containing reduced sulfur that is synthesized in the last stage of plant photosynthetic assimilation of sulfate. It is a very important metabolite not only because it is crucial for the structure, function and regulation of proteins but also because it is the precursor molecule of an enormous number of sulfur-containing metabolites essential for plant health and development. The biosynthesis of Cys is accomplished by the sequential reaction of serine acetyltransferase (SAT) and O-acetylserine(thiol)synthase (OASTL). In Arabidopsis thaliana, the analysis of specific mutants of members of the SAT and OASTL families has demonstrated that the cytosol is the compartment where the bulk of Cys synthesis takes place and that the cytosolic OASTL enzyme OAS-A1 is the responsible enzyme. Another member of the OASTL family is DES1, a novel l-cysteine desulfhydrase that catalyzes the desulfuration of Cys to produce sulfide, thus acting in a manner opposite to that of OAS-A1. Detailed studies of the oas-a1 and des1 null mutants have revealed the involvement of the DES1 and OAS-A1 proteins in coordinate regulation of Cys homeostasis and the generation of sulfide in the cytosol for signaling purposes. Thus, the levels of Cys in the cytosol strongly affect plant responses to both abiotic and biotic stress conditions, while sulfide specifically generated from the degradation of Cys negatively regulates autophagy induced in different situations. In conclusion, modulation of the levels of Cys and sulfide is likely critical for plant performance. 相似文献
6.
The molecular mechanism of light signal transduction in plants mediated by the photosensor phytochrome is not well understood. The possibility that phytochrome initiates the signal transduction chain by modulating a G-protein-like receptor is examined in the present work. Etiolated Avena seedlings contain G-proteins as examined in terms of the binding of GTP as well as by cross-reaction with mammalian G-protein antibodies. The binding of GTP was regulated in vivo by red/far-red light. The possible involvement of G-proteins in the phytochrome-mediated signal transduction in etiolated Avena seedlings has been implicated from the study of the light regulated expression of the Cab and phy genes. 相似文献
7.
8.
Chenxi Gao Guangming Chen Guillermo Romero Stergios Moschos Xiang Xu Jing Hu 《The Journal of biological chemistry》2014,289(10):7099-7108
A pivotal step in canonical Wnt signaling is Wnt-induced β-catenin stabilization. In the absence of Wnt, β-catenin is targeted for β-transducin repeats-containing proteins (β-TrCP)-mediated degradation due to phosphorylation by glycogen synthase kinase 3 (Gsk3). How canonical Wnt signaling regulates Gsk3 to inhibit β-catenin proteolysis remains largely elusive. This study reveals novel key molecular events in Wnt signaling: induction of Gsk3β ubiquitination and Gsk3β-β-TrCP binding. We found that Wnt stimulation induced prolonged monoubiquitination of Gsk3β and Gsk3β-β-TrCP interaction. Monoubiquitination did not cause Gsk3β degradation nor affects its enzymatic activity. Rather, increased monoubiquitination of Gsk3β/Gsk3β-β-TrCP association suppressed β-catenin recruitment of β-TrCP, leading to long-term inhibition of β-catenin ubiquitination and degradation. 相似文献
9.
10.