全文获取类型
收费全文 | 600篇 |
免费 | 55篇 |
出版年
2021年 | 2篇 |
2018年 | 4篇 |
2017年 | 5篇 |
2016年 | 9篇 |
2015年 | 20篇 |
2014年 | 22篇 |
2013年 | 32篇 |
2012年 | 27篇 |
2011年 | 25篇 |
2010年 | 30篇 |
2009年 | 33篇 |
2008年 | 21篇 |
2007年 | 26篇 |
2006年 | 23篇 |
2005年 | 26篇 |
2004年 | 25篇 |
2003年 | 22篇 |
2002年 | 14篇 |
2001年 | 18篇 |
2000年 | 18篇 |
1999年 | 12篇 |
1998年 | 15篇 |
1997年 | 15篇 |
1996年 | 7篇 |
1995年 | 13篇 |
1994年 | 8篇 |
1993年 | 14篇 |
1992年 | 8篇 |
1991年 | 14篇 |
1990年 | 8篇 |
1989年 | 10篇 |
1988年 | 10篇 |
1987年 | 4篇 |
1986年 | 7篇 |
1985年 | 12篇 |
1984年 | 11篇 |
1983年 | 6篇 |
1982年 | 17篇 |
1981年 | 6篇 |
1980年 | 3篇 |
1979年 | 6篇 |
1978年 | 7篇 |
1977年 | 8篇 |
1976年 | 6篇 |
1975年 | 7篇 |
1973年 | 5篇 |
1972年 | 2篇 |
1969年 | 2篇 |
1968年 | 2篇 |
1950年 | 2篇 |
排序方式: 共有655条查询结果,搜索用时 515 毫秒
181.
182.
Davidson WS Koop BF Jones SJ Iturra P Vidal R Maass A Jonassen I Lien S Omholt SW 《Genome biology》2010,11(9):403
The International Collaboration to Sequence the Atlantic Salmon Genome (ICSASG) will produce a genome sequence that identifies
and physically maps all genes in the Atlantic salmon genome and acts as a reference sequence for other salmonids. 相似文献
183.
Steven JM Jones Janessa Laskin Yvonne Y Li Obi L Griffith Jianghong An Mikhail Bilenky Yaron S Butterfield Eric Chuah Richard Corbett Anthony Fejes Simon Chan Nancy Liao Katayoon Kasaian Malachi Griffith John Yee Montgomery Martin Michael Mayo Nataliya Melnyk Ryan D Morin Trevor J Pugh Tesa Severson Sohrab P Shah Margaret Sutcliffe Angela Tam Jefferson Terry Nina Thiessen Thomas Thomson Richard Varhol Thomas Zeng Yongjun Zhao Richard A Moore David G Huntsman Inanc Birol Martin Hirst Robert A Holt Marco A Marra 《Genome biology》2010,11(Z1):I5
184.
Steven JM Jones Janessa Laskin Yvonne Y Li Obi L Griffith Jianghong An Mikhail Bilenky Yaron S Butterfield Timothee Cezard Eric Chuah Richard Corbett Anthony P Fejes Malachi Griffith John Yee Montgomery Martin Michael Mayo Nataliya Melnyk Ryan D Morin Trevor J Pugh Tesa Severson Sohrab P Shah Margaret Sutcliffe Angela Tam Jefferson Terry Nina Thiessen Thomas Thomson Richard Varhol Thomas Zeng Yongjun Zhao Richard A Moore David G Huntsman Inanc Birol Martin Hirst Robert A Holt Marco A Marra 《Genome biology》2010,11(8):1-12
Background
Adenocarcinomas of the tongue are rare and represent the minority (20 to 25%) of salivary gland tumors affecting the tongue. We investigated the utility of massively parallel sequencing to characterize an adenocarcinoma of the tongue, before and after treatment.Results
In the pre-treatment tumor we identified 7,629 genes within regions of copy number gain. There were 1,078 genes that exhibited increased expression relative to the blood and unrelated tumors and four genes contained somatic protein-coding mutations. Our analysis suggested the tumor cells were driven by the RET oncogene. Genes whose protein products are targeted by the RET inhibitors sunitinib and sorafenib correlated with being amplified and or highly expressed. Consistent with our observations, administration of sunitinib was associated with stable disease lasting 4 months, after which the lung lesions began to grow. Administration of sorafenib and sulindac provided disease stabilization for an additional 3 months after which the cancer progressed and new lesions appeared. A recurring metastasis possessed 7,288 genes within copy number amplicons, 385 genes exhibiting increased expression relative to other tumors and 9 new somatic protein coding mutations. The observed mutations and amplifications were consistent with therapeutic resistance arising through activation of the MAPK and AKT pathways.Conclusions
We conclude that complete genomic characterization of a rare tumor has the potential to aid in clinical decision making and identifying therapeutic approaches where no established treatment protocols exist. These results also provide direct in vivo genomic evidence for mutational evolution within a tumor under drug selection and potential mechanisms of drug resistance accrual. 相似文献185.
Ori Elkayam Refael Segal Daniele Bendayan Robert van Uitert Carla Onnekink Ger JM Pruijn 《Arthritis research & therapy》2010,12(1):R12
Introduction
Patients with tuberculosis (TB) frequently produce anti-citrullinated protein antibodies (ACPA). The objective of this study is to characterize the citrulline-dependence of the ACPA reactivity in sera of patients with mycobacterium infections. 相似文献186.
187.
Plasmid evolution and interaction between the plasmid addiction stability systems of two related broad-host-range IncQ-like plasmids
下载免费PDF全文
![点击此处可从《Journal of bacteriology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Plasmid pTC-F14 contains a plasmid stability system called pas (plasmid addiction system), which consists of two proteins, a PasA antitoxin and a PasB toxin. This system is closely related to the pas of plasmid pTF-FC2 (81 and 72% amino acid identity for PasA and PasB, respectively) except that the pas of pTF-FC2 contains a third protein, PasC. As both pTC-F14 and pTF-FC2 are highly promiscuous broad-host-range plasmids isolated from bacteria that share a similar ecological niche, the plasmids are likely to encounter each other. We investigated the relative efficiencies of the two stability systems and whether they had evolved apart sufficiently for each pas to stabilize a plasmid in the presence of the other. The three-component pTF-FC2 pas was more efficient at stabilization of a heterologous tester plasmid than the two component pas of pTC-F14 in Escherichia coli host cells (+/- 92% and +/- 60% after 100 generations, respectively). The PasA antidote of each pas was unable to neutralize the PasB toxin of the other plasmid. The pas proteins of each plasmid autoregulated their own expression as well as that of the pas of the other plasmid. The pas of pTF-FC2 was more effective at repressing the pas operon of pTC-F14 than the pas of pTC-F14 was able to repress itself or the pas of pTF-FC2. This increased efficiency was not due to the PasC of pTF-FC2. The effect of this stronger repression was that pTF-FC2 displaced pTC-F14 when the two plasmids were coresident in the same E. coli host cell. Plasmid curing resulted in the arrest of cell growth but did not cause cell death, and plasmid stability was not influenced by the E. coli mazEF genes. 相似文献
188.
189.
Chun HH Cary RB Lansigan F Whitelegge J Rawlings DJ Gatti RA 《Biochemical and biophysical research communications》2004,322(1):74-81
The ataxia-telangiectasia mutated (ATM) gene product plays a role in responding to double stand DNA breaks. Some biochemical studies of ATM function have been hampered by lack of an efficient expression system and abundant purified ATM protein. We report the construction of a vaccinia virus expressing ATM, vWR-ATM, which was used to produce large amounts of functional FLAG-tagged ATM protein (FLAG-ATM) in HeLa cells. Kinase activity of the purified FLAG-ATM was dependent on manganese and inhibited with wortmannin. Using the FLAG-ATM recombinant protein, GST-p53 serine 15 phosphorylation increased in the presence of damaged DNA. PHAS-1 phosphorylation was found to be DNA independent. Purified FLAG-ATM was recovered in the autophosphorylated form, as demonstrated by phosphorylation of ATM serine 1981. As shown by atomic force microscopy, FLAG-ATM bound to linear DNA both at broken ends and in mid-strands. Vaccinia virus is the most efficient ATM expression system described to date. 相似文献
190.
Kawakami Y Nishimoto H Kitaura J Maeda-Yamamoto M Kato RM Littman DR Leitges M Rawlings DJ Kawakami T 《The Journal of biological chemistry》2004,279(46):47720-47725
Akt (= protein kinase B), a subfamily of the AGC serine/threonine kinases, plays critical roles in survival, proliferation, glucose metabolism, and other cellular functions. Akt activation requires the recruitment of the enzyme to the plasma membrane by interacting with membrane-bound lipid products of phosphatidylinositol 3-kinase. Membrane-bound Akt is then phosphorylated at two sites for its full activation; Thr-308 in the activation loop of the kinase domain is phosphorylated by 3-phosphoinositide-dependent kinase-1 (PDK1) and Ser-473 in the C-terminal hydrophobic motif by a putative kinase PDK2. The identity of PDK2 has been elusive. Here we present evidence that conventional isoforms of protein kinase C (PKC), particularly PKCbetaII, can regulate Akt activity by directly phosphorylating Ser-473 in vitro and in IgE/antigen-stimulated mast cells. By contrast, PKCbeta is not required for Ser-473 phosphorylation in mast cells stimulated with stem cell factor or interleukin-3, in serum-stimulated fibroblasts, or in antigen receptor-stimulated T or B lymphocytes. Therefore, PKCbetaII appears to work as a cell type- and stimulus-specific PDK2. 相似文献