全文获取类型
收费全文 | 676篇 |
免费 | 36篇 |
专业分类
712篇 |
出版年
2023年 | 3篇 |
2022年 | 21篇 |
2021年 | 27篇 |
2020年 | 10篇 |
2019年 | 16篇 |
2018年 | 14篇 |
2017年 | 12篇 |
2016年 | 23篇 |
2015年 | 31篇 |
2014年 | 34篇 |
2013年 | 39篇 |
2012年 | 49篇 |
2011年 | 46篇 |
2010年 | 29篇 |
2009年 | 29篇 |
2008年 | 44篇 |
2007年 | 29篇 |
2006年 | 19篇 |
2005年 | 19篇 |
2004年 | 19篇 |
2003年 | 21篇 |
2002年 | 16篇 |
2001年 | 12篇 |
2000年 | 14篇 |
1999年 | 13篇 |
1998年 | 4篇 |
1997年 | 6篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 7篇 |
1990年 | 4篇 |
1989年 | 7篇 |
1988年 | 5篇 |
1987年 | 7篇 |
1986年 | 5篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1982年 | 6篇 |
1981年 | 4篇 |
1980年 | 5篇 |
1978年 | 4篇 |
1977年 | 3篇 |
1976年 | 7篇 |
1975年 | 3篇 |
1974年 | 3篇 |
1971年 | 3篇 |
1968年 | 2篇 |
1965年 | 2篇 |
排序方式: 共有712条查询结果,搜索用时 46 毫秒
111.
112.
Sexual size dimorphism (SSD) is often assumed to be driven by three major selective processes: (1) sexual selection influencing male size and thus mating success, (2) fecundity selection acting on females and (3) inter‐sexual resource division favouring different size in males and females to reduce competition for resources. Sexual selection should be particularly strong in species that exhibit lek polygyny, since male mating success is highly skewed in such species. We investigated whether these three selective processes are related to SSD evolution in grouse and allies (Phasianidae). Male‐biased SSD increased with body size (Rensch’s rule) and lekking species exhibited more male‐biased SSD than nonlekking ones. Directional phylogenetic analyses indicated that lekking evolved before SSD, but conclusions were highly dependent on the body size traits and chosen model values. There was no relationship between SSD and male display agility, nor did resource division influence SSD. Although clutch mass increased with female body size it was not related to the degree of SSD. Taken together, the results are most consistent with the hypothesis that lekking behaviour led to the evolution of male‐biased SSD in Phasianidae. 相似文献
113.
JoAnne Montalbano Ki Lui M. Saeed Sheikh Ying Huang 《The Journal of biological chemistry》2009,284(27):18129-18142
Recently, we reported the identification of a novel gene named RBEL1 (Rab-like protein 1) and characterized its two encoded isoforms, RBEL1A and RBEL1B, that function as novel GTPases of Ras superfamily. Here we report the identification of two additional splice variants of RBEL1 that we have named RBEL1C and -D. All four RBEL1 isoforms (A, B, C, and D) have identical N termini harboring the Rab-like GTPase domains but contain variable C termini. Although all isoforms can be detected in both cytoplasm and nucleus, RBEL1A is predominantly cytoplasmic, whereas RBEL1B is mostly nuclear. RBEL1C and -D, by contrast, are evenly distributed between the cytoplasm and nucleus. Furthermore, all four RBEL1 proteins are also capable of associating with cellular membrane. The RBEL1 proteins also exhibit a unique nucleotide-binding potential and, whereas the larger A and B isoforms are mainly GTP-bound, the smaller C and D variants bind to both GTP and GDP. Furthermore, a regulatory region at amino acid position 236–302 immediately adjacent to the GTP-binding domain is important for GTP-binding potential of RBEL1A, because deletion of this region converts RBEL1A from predominantly GTP-bound to GDP-bound. RBEL1 knockdown via RNA interference results in marked cell growth suppression, which is associated with morphological and biochemical features of apoptosis as well as inhibition of extracellular signal-regulated kinase phosphorylation. Taken together, our results indicate that RBEL1 proteins are linked to cell growth and survival and possess unique biochemical, cellular, and functional characteristics and, therefore, appear to form a novel subfamily of GTPases within the Ras superfamily.The Ras superfamily is known to comprise five structurally distinct subfamilies of small GTPases, including Ras, Rho, Rab, Sar1/Arf, and Ran, and each subfamily of these GTPases possess distinct functions in the regulation of a variety of cellular processes such as cell proliferation, cell differentiation, cytoskeletal organization, protein transport, and trafficking (1–4). The Ras subfamily of GTPases (N-, H-, and K-Ras) function predominantly in relaying signals from receptors at the plasma membrane and modulating cell signaling pathways that regulate cell proliferation, differentiation, and survival (5). Ran GTPase, on other hand, is a key regulator of nucleocytoplasmic transport that regulates protein transport across the nuclear pore complex (6, 7). The Rab subfamily is the largest subfamily among the Ras superfamily and contains more than 60 members. The key functions of the Rab GTPases are to regulate protein exocytic and endocytic pathways and modulate intracellular protein transport/trafficking (8–13).In general, the Ras superfamily GTPases cycle between an active GTP-bound state and an inactive GDP-bound state. There are five N-terminal motifs involved in the binding and hydrolysis of GTP that are highly conserved among all GTPases: G1 (GXXXXGK(S/T)), G2 (T), G3 (DXXG), G4 ((N/T)(K/Q)XD), and G5 (EXSAX). Each sequence has particular functions involved in binding nucleotides (GTP or GDP) and facilitating hydrolysis (4, 14, 15). In general, the intrinsic GTPase activity (converting GTP to GDP) and exchange of GDP for GTP are slow processes for these GTPases and thus require regulatory proteins such as GTPase-activating proteins and GDP/GTP exchange factors to facilitate these processes (16–18).For the last two decades, the Ras superfamily has been a major focus in the cancer field as many of the members are either mutated or dysregulated in cancer. The founding members of the Ras superfamily, H-Ras and K-Ras, were first identified as viral oncogenes (1, 4). Later studies demonstrated that mutations of the Ras proteins (H-, N-, and K-Ras) occur frequently in human cancers, and the mutations identified are mostly clustered within the GTP-binding domains of the proteins thus locking Ras proteins in a GTP-bound configuration. GTP-bound Ras is constitutively active; it constantly activates its effector proteins to transduce cell proliferative signals (1, 4). Unlike Ras subfamily genes, mutations occurring in Rab and Rab-like genes are less common, yet alterations in gene expression of a number of Rab genes have been reported in multiple human malignancies. For example, Rab25 overexpression has been linked to prostate cancer progression (19). Rab2 overexpression has been found in lung adenomas and adenocarcinomas (20). In addition, alterations in Rab gene expression have also been linked to cancer drug resistance. For instance, resistance to the anticancer drug doxorubicin in MCF-7 cells has been linked with reduced expression of Rab6C, and introduction of exogenous Rab6C restores drug sensitivity (21).We have recently reported the identification two novel Ras superfamily GTPases, RBEL1A and RBEL1B (22). RBEL1A and RBEL1B are two splice variants of the RBEL1 gene and are highly homologous to the Rab and Ran GTPases within their N-terminal GTP-binding domains (22). Our studies show that both RBEL1A and -B predominantly bind to GTP. A single point mutation (T57N) in the GTP-binding domain of RBEL1A and -B abolishes their ability to bind to both GTP and GDP. Both RBEL1A and RBEL1B localize in the nucleus as well as in the cytosol. Whereas RBEL1A is predominantly cytosolic, RBEL1B is primarily nuclear. Interestingly, our studies also suggested that nucleotide (GTP or GDP)-binding could be important for the nuclear distribution of RBEL1B, because the nucleotide binding-deficient mutant form (T57N) of RBEL1B did not reside in the nucleus but rather became largely cytosolic (22).In our continuous efforts to fully elucidate the function of RBEL1, we have identified two additional splice variants that we have named RBEL1C and RBEL1D. Here we report further characterization of all four RBEL1 splice variants in terms of their GTPase activities, subcellular localizations, regulations, and potential functions. Our results indicate that RBEL1 GTPases, although sharing some common features with other Ras superfamily members, also harbor unique characteristics that are significantly different from other Ras superfamily GTPases. Based on our findings, we suggest that RBEL1 proteins appear to form a novel subfamily of GTPases within the Ras superfamily. 相似文献
114.
115.
116.
Ashley MV Caballero IC Chaovalitwongse W Dasgupta B Govindan P Sheikh SI Berger-Wolf TY 《Molecular ecology resources》2009,9(4):1127-1131
A software suite KINALYZER reconstructs full-sibling groups without parental information using data from codominant marker loci such as microsatellites. KINALYZER utilizes a new algorithm for sibling reconstruction in diploid organisms based on combinatorial optimization. KINALYZER makes use of a Minimum 2-Allele Set Cover approach based on Mendelian inheritance rules and finds the smallest number of sibling groups that contain all the individuals in the sample. Also available is a 'Greedy Consensus' approach that reconstructs sibgroups using subsets of loci and finds the consensus of the partial solutions. Unlike likelihood methods for sibling reconstruction, KINALYZER does not require information about population allele frequencies and it makes no assumptions regarding the mating system of the species. KINALYZER is freely available as a web-based service. 相似文献
117.
In Malaysia, tissue banking activities began in Universiti Sains Malaysia (USM) Tissue Bank in early 1990s. Since then a few
other bone banks have been set up in other government hospitals and institutions. However, these banks are not governed by
the national authority. In addition there is no requirement set by the national regulatory authority on coding and traceability
for donated human tissues for transplantation. Hence, USM Tissue Bank has taken the initiatives to adopt a system that enables
the traceability of tissues between the donor, the processed tissue and the recipient based on other international standards
for tissue banks. The traceability trail has been effective and the bank is certified compliance to the international standard
ISO 9001:2008. 相似文献
118.
Muse Oke Lester G. Carter Kenneth A. Johnson Huanting Liu Stephen A. McMahon Xuan Yan Melina Kerou Nadine D. Weikart Nadia Kadi Md. Arif Sheikh Stefan Schmelz Mark Dorward Michal Zawadzki Christopher Cozens Helen Falconer Helen Powers Ian M. Overton C. A. Johannes van Niekerk Xu Peng Prakash Patel Roger A. Garrett David Prangishvili Catherine H. Botting Peter J. Coote David T. F. Dryden Geoffrey J. Barton Ulrich Schwarz-Linek Gregory L. Challis Garry L. Taylor Malcolm F. White James H. Naismith 《Journal of structural and functional genomics》2010,11(2):167-180
The Scottish Structural Proteomics Facility was funded to develop a laboratory scale approach to high throughput structure determination. The effort was successful in that over 40 structures were determined. These structures and the methods harnessed to obtain them are reported here. This report reflects on the value of automation but also on the continued requirement for a high degree of scientific and technical expertise. The efficiency of the process poses challenges to the current paradigm of structural analysis and publication. In the 5 year period we published ten peer-reviewed papers reporting structural data arising from the pipeline. Nevertheless, the number of structures solved exceeded our ability to analyse and publish each new finding. By reporting the experimental details and depositing the structures we hope to maximize the impact of the project by allowing others to follow up the relevant biology. 相似文献
119.
Khurram Mushtaq Sathi Babu Chodisetti Pradeep K. Rai Sudeep K. Maurya Mohammed Amir Javaid A. Sheikh Javed N. Agrewala 《Amino acids》2014,46(5):1265-1274
CD4 T cells play a cardinal role in orchestrating immune system. Differentiation of CD4 T cells to Th1 and Th2 effector subsets depends on multiple factors such as relative intensity of interactions between T cell receptor with peptide-major histocompatibility complex, cytokine milieu, antigen dose, and costimulatory molecules. Literature supports the critical role of peptide’s binding affinity to Human Leukocyte Antigens (HLAs) and in the differentiation of naïve CD4 T cells to Th1 and Th2 subsets. However, there exists no definite report addressing very precisely the correlation between physicochemical properties (hydrophobicity, hydrophilicity), pattern, position of amino acids in peptide and their role in skewing immune response towards Th1 and Th2 cells. This may play a significant role in designing peptide vaccines. Hence in the present study, we have evaluated the relationship between amino acid pattern and their influence in differentiation of Th1 and Th2 cells. We have used a data set of 320 peptides, whose role has been already established experimentally in the generation of either Th1 or Th2 immune response. Further, characterization was done based on binding affinity, promiscuity, amino acid pattern and binding conformation of peptides. We have observed that distinct amino acids in peptides elicit either Th1 or Th2 immunity. Consequently, this study signifies that alteration in the sequence and type of selected amino acids in the HLA class II binding peptides can modulate the differentiation of Th1 and Th2 cells. Therefore, this study may have an important implication in providing a platform for designing peptide-based vaccine candidates that can trigger desired Th1 or Th2 response. 相似文献
120.
Douglas?L?ArnoldEmail author Peter?A?Calabresi Bernd?C?Kieseier Sarah?I?Sheikh Aaron?Deykin Ying?Zhu Shifang?Liu Xiaojun?You Bjoern?Sperling Serena?Hung 《BMC neurology》2014,14(1):240