全文获取类型
收费全文 | 602篇 |
免费 | 27篇 |
国内免费 | 2篇 |
出版年
2023年 | 6篇 |
2022年 | 16篇 |
2021年 | 29篇 |
2020年 | 9篇 |
2019年 | 23篇 |
2018年 | 26篇 |
2017年 | 24篇 |
2016年 | 28篇 |
2015年 | 34篇 |
2014年 | 36篇 |
2013年 | 30篇 |
2012年 | 41篇 |
2011年 | 52篇 |
2010年 | 24篇 |
2009年 | 12篇 |
2008年 | 21篇 |
2007年 | 23篇 |
2006年 | 26篇 |
2005年 | 14篇 |
2004年 | 11篇 |
2003年 | 16篇 |
2002年 | 17篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 2篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1994年 | 12篇 |
1993年 | 11篇 |
1992年 | 5篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 6篇 |
1988年 | 6篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1967年 | 2篇 |
1964年 | 3篇 |
1960年 | 1篇 |
1959年 | 4篇 |
1936年 | 1篇 |
排序方式: 共有631条查询结果,搜索用时 265 毫秒
71.
72.
Poliovirus causes flaccid paralysis through the destruction of motor neurons in the CNS. Susceptibility to its infection is mainly due
to the interaction in between the surface capsid proteins and its receptors on the host cell surface, important for binding,
penetration and other necessary events during early infection. Receptor modification is a new approach to treat viral diseases by
the modification of target proteins structure. Binding domains are modified in an effective way to make it difficult for the virus to
recognize it. In this study, tolerant and intolerant induced mutations in the poliovirus receptor, VP1 and VP2 were identified and
substituted in the seed sequence to get the modified versions. Substitutions causing changes in initial folding were short listed and
further analyzed for high level folding, physiochemical properties and interactions. Highest RMSD values were observed in
between the seed and the mutant K90F (3.265 Å) and Q130W (3.270Å) respectively. The proposed substitutions were found to have
low functional impact and thus can be further tested and validated by the experimental researchers. Interactions analyses proved
most of the substitutions having decreased affinity for both the VP1 and VP2 and thus are of significant importance against
poliovirus. This study will play an important role for bridging computational biology to other fields of applied biology and also
will provide an insight to develop resistance against viral diseases. It is also expected that same approach can also be applicable
against other viruses like HCV, HIV and other in near future. 相似文献
73.
Rueda P Balabanian K Lagane B Staropoli I Chow K Levoye A Laguri C Sadir R Delaunay T Izquierdo E Pablos JL Lendinez E Caruz A Franco D Baleux F Lortat-Jacob H Arenzana-Seisdedos F 《PloS one》2008,3(7):e2543
The CXCL12gamma chemokine arises by alternative splicing from Cxcl12, an essential gene during development. This protein binds CXCR4 and displays an exceptional degree of conservation (99%) in mammals. CXCL12gamma is formed by a protein core shared by all CXCL12 isoforms, extended by a highly cationic carboxy-terminal (C-ter) domain that encompass four overlapped BBXB heparan sulfate (HS)-binding motifs. We hypothesize that this unusual domain could critically determine the biological properties of CXCL12gamma through its interaction to, and regulation by extracellular glycosaminoglycans (GAG) and HS in particular. By both RT-PCR and immunohistochemistry, we mapped the localization of CXCL12gamma both in mouse and human tissues, where it showed discrete differential expression. As an unprecedented feature among chemokines, the secreted CXCL12gamma strongly interacted with cell membrane GAG, thus remaining mostly adsorbed on the plasmatic membrane upon secretion. Affinity chromatography and surface plasmon resonance allowed us to determine for CXCL12gamma one of the higher affinity for HS (K(d) = 0.9 nM) ever reported for a protein. This property relies in the presence of four canonical HS-binding sites located at the C-ter domain but requires the collaboration of a HS-binding site located in the core of the protein. Interestingly, and despite reduced agonist potency on CXCR4, the sustained binding of CXCL12gamma to HS enabled it to promote in vivo intraperitoneal leukocyte accumulation and angiogenesis in matrigel plugs with much higher efficiency than CXCL12alpha. In good agreement, mutant CXCL12gamma chemokines selectively devoid of HS-binding capacity failed to promote in vivo significant cell recruitment. We conclude that CXCL12gamma features unique structural and functional properties among chemokines which rely on the presence of a distinctive C-ter domain. The unsurpassed capacity to bind to HS on the extracellular matrix would make CXCL12gamma the paradigm of haptotactic proteins, which regulate essential homeostatic functions by promoting directional migration and selective tissue homing of cells. 相似文献
74.
Patricia Rueda Karl Balabanian Bernard Lagane Isabelle Staropoli Ken Chow Angelique Levoye Cedric Laguri Rabia Sadir Thierry Delaunay Elena Izquierdo Jose Luis Pablos Elena Lendinez Antonio Caruz Diego Franco Fran?oise Baleux Hugues Lortat-Jacob Fernando Arenzana-Seisdedos 《PloS one》2008,3(7)
The CXCL12γ chemokine arises by alternative splicing from Cxcl12, an essential gene during development. This protein binds CXCR4 and displays an exceptional degree of conservation (99%) in mammals. CXCL12γ is formed by a protein core shared by all CXCL12 isoforms, extended by a highly cationic carboxy-terminal (C-ter) domain that encompass four overlapped BBXB heparan sulfate (HS)-binding motifs. We hypothesize that this unusual domain could critically determine the biological properties of CXCL12γ through its interaction to, and regulation by extracellular glycosaminoglycans (GAG) and HS in particular. By both RT-PCR and immunohistochemistry, we mapped the localization of CXCL12γ both in mouse and human tissues, where it showed discrete differential expression. As an unprecedented feature among chemokines, the secreted CXCL12γ strongly interacted with cell membrane GAG, thus remaining mostly adsorbed on the plasmatic membrane upon secretion. Affinity chromatography and surface plasmon resonance allowed us to determine for CXCL12γ one of the higher affinity for HS (Kd = 0.9 nM) ever reported for a protein. This property relies in the presence of four canonical HS-binding sites located at the C-ter domain but requires the collaboration of a HS-binding site located in the core of the protein. Interestingly, and despite reduced agonist potency on CXCR4, the sustained binding of CXCL12γ to HS enabled it to promote in vivo intraperitoneal leukocyte accumulation and angiogenesis in matrigel plugs with much higher efficiency than CXCL12α. In good agreement, mutant CXCL12γ chemokines selectively devoid of HS-binding capacity failed to promote in vivo significant cell recruitment. We conclude that CXCL12γ features unique structural and functional properties among chemokines which rely on the presence of a distinctive C-ter domain. The unsurpassed capacity to bind to HS on the extracellular matrix would make CXCL12γ the paradigm of haptotactic proteins, which regulate essential homeostatic functions by promoting directional migration and selective tissue homing of cells. 相似文献
75.
76.
77.
78.
Emilia Rabia Vronique Garambois Julie Hubert Marine Bruciamacchie Nelly Pirot Hlne Delpech Morgane Broyon Charles Theillet Pierre-Emmanuel Colombo Nadia Vie Diego Tosi Celine Gongora Lakhdar Khellaf Marta Jarlier Nina Radosevic-Robin Thierry Chards Andr Plegrin Christel Larbouret 《MABS-AUSTIN》2021,13(1)
79.
Perveen Sumera Khan Tehmina Ahsan Shaheen Humaira Naz Rabia Hyder Muhammad Zeeshan Ijaz Bushra Naqvi S. M. Saqlan Yasmin Tayyaba 《In vitro cellular & developmental biology. Plant》2021,57(6):907-922
In Vitro Cellular & Developmental Biology - Plant - The OsRGLP1 gene was overexpressed under the control of CaMV 35S promoter in tomato (Solanum lycopersicum L.) plants using... 相似文献
80.
Xinshou Ouyang Sheng-Na Han Ji-Yuan Zhang Evangelos Dioletis Balazs Tamas Nemeth Pal Pacher Dechun Feng Ramon Bataller Joaquin Cabezas Peter Stärkel Joan Caballeria Rebecca LePine Pongratz Shi-Ying Cai Bernd Schnabl Rafaz Hoque Yonglin Chen Wei-hong Yang Irma Garcia-Martinez Wajahat Zafar Mehal 《Cell metabolism》2018,27(2):339-350.e3