全文获取类型
收费全文 | 159篇 |
免费 | 11篇 |
国内免费 | 1篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 5篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 7篇 |
2017年 | 2篇 |
2016年 | 1篇 |
2015年 | 6篇 |
2014年 | 7篇 |
2013年 | 7篇 |
2012年 | 13篇 |
2011年 | 12篇 |
2010年 | 9篇 |
2009年 | 12篇 |
2008年 | 10篇 |
2007年 | 7篇 |
2006年 | 6篇 |
2005年 | 1篇 |
2004年 | 4篇 |
2003年 | 4篇 |
2002年 | 1篇 |
2001年 | 3篇 |
2000年 | 1篇 |
1999年 | 5篇 |
1998年 | 7篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1983年 | 3篇 |
1982年 | 5篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1970年 | 2篇 |
排序方式: 共有171条查询结果,搜索用时 125 毫秒
1.
2.
Germ-Line Mutations in the von Hippel–Lindau Tumor-Suppressor Gene Are Similar to Somatic von Hippel–Lindau Aberrations in Sporadic Renal Cell Carcinoma 下载免费PDF全文
Jean M. Whaley Joseph Naglich Lawrence Gelbert Y. Edward Hsia James M. Lamiell Jane S. Green Debra Collins Hartmut P. H. Neumann Jana Laidlaw Fred P. Li Andres J. P. Klein-Szanto Bernd R. Seizinger Nikolai Kley 《American journal of human genetics》1994,55(6):1092-1102
von Hippel–Lindau (VHL) disease is a hereditary tumor syndrome predisposing to multifocal bilateral renal cell carcinomas (RCCs), pheochromocytomas, and pancreatic tumors, as well as angiomas and hemangioblastomas of the CNS. A candidate gene for VHL was recently identified, which led to the isolation of a partial cDNA clone with extended open reading frame, without significant homology to known genes or obvious functional motifs, except for an acidic pentamer repeat domain. To further characterize the functional domains of the VHL gene and assess its involvement in hereditary and nonhereditary tumors, we performed mutation analyses and studied its expression in normal and tumor tissue. We identified germ-line mutations in 39% of VHL disease families. Moreover, 33% of sporadic RCCs and all (6/6) sporadic RCC cell lines analyzed showed mutations within the VHL gene. Both germ-line and somatic mutations included deletions, insertions, splice-site mutations, and missense and nonsense mutations, all of which clustered at the 3' end of the corresponding partial VHL cDNA open reading frame, including an alternatively spliced exon 123 nt in length, suggesting functionally important domains encoded by the VHL gene in this region. Over 180 sporadic tumors of other types have shown no detectable base changes within the presumed coding sequence of the VHL gene to date. We conclude that the gene causing VHL has an important and specific role in the etiology of sporadic RCCs, acts as a recessive tumor-suppressor gene, and appears to encode important functional domains within the 3' end of the known open reading frame. 相似文献
3.
Direct sequencing of the mitochondrial displacement loop (D-loop) of shrews
(genus Sorex) for the region between the tRNA(Pro) and the conserved
sequence block-F revealed variable numbers of 79-bp tandem repeats. These
repeats were found in all 19 individuals sequenced, representing three
subspecies and one closely related species of the masked shrew group (Sorex
cinereus cinereus, S. c. miscix, S. c. acadicus, and S. haydeni) and an
outgroup, the pygmy shrew (S. hoyi). Each specimen also possessed an
adjacent 76-bp imperfect copy of the tandem repeats. One individual was
heteroplasmic for length variants consisting of five and seven copies of
the 79-bp tandem repeat. The sequence of the repeats is conducive to the
formation of secondary structure. A termination-associated sequence is
present in each of the repeats and in a unique sequence region 5' to the
tandem array as well. Mean genetic distance between the masked shrew taxa
and the pygmy shrew was calculated separately for the unique sequence
region, one of the tandem repeats, the imperfect repeat, and these three
regions combined. The unique sequence region evolved more rapidly than the
tandem repeats or the imperfect repeat. The small genetic distance between
pairs of tandem repeats within an individual is consistent with a model of
concerted evolution. Repeats are apparently duplicated and lost at a high
rate, which tends to homogenize the tandem array. The rate of D- loop
sequence divergence between the masked and pygmy shrews is estimated to be
15%-20%/Myr, the highest rate observed in D-loops of mammals. Rapid
sequence evolution in shrews may be due either to their high metabolic rate
and short generation time or to the presence of variable numbers of tandem
repeats.
相似文献
4.
5.
大鼠胼胝体内神经肽Y免疫反应阳性纤维的发育 总被引:1,自引:0,他引:1
本实验用免疫组织化学ABC法研究了大鼠胼胝体内神经肽Y免疫反应阳性(NPY-IR)纤维的生后发育。结果发现,许多NPY-IR纤维在大鼠出生时便存在于胼胝体内。NPY-IR胼胝体纤维的密度在生后1周内继续逐渐增高,在第2周内达到最高峰。之后,NPY-IR胼胝体纤维的密度逐渐下降,至第3周末时接近成年时的水平,即仅有少量NPY-IR纤维存在于胼胝体内。这些结果提示在大鼠早期生后发育过程中许多NPY-IR胼胝体纤维是暂时性的,其作用可能与大脑皮质的机能发育有关。 相似文献
6.
7.
8.
9.
Black AP Bhayani H Ryder CA Pugh MT Gardner-Medwin JM Southwood TR 《Arthritis research & therapy》2003,5(5):R277-R284
The aim of this research was to determine whether all memory T cells have the same propensity to migrate to the joint in patients
with juvenile idiopathic arthritis. Paired synovial fluid and peripheral blood mononuclear cell proliferative responses to
a panel of antigens were measured and the results correlated with a detailed set of laboratory and clinical data from 39 patients
with juvenile idiopathic arthritis. Two distinct patterns of proliferative response were found in the majority of patients:
a diverse pattern, in which synovial fluid responses were greater than peripheral blood responses for all antigens tested;
and a restricted pattern, in which peripheral blood responses to some antigens were more vigorous than those in the synovial
fluid compartment. The diverse pattern was generally found in patients with a high acute phase response, whereas patients
without elevated acute phase proteins were more likely to demonstrate a restricted pattern. We propose that an association
between the synovial fluid T cell repertoire and the acute phase response suggests that proinflammatory cytokines may influence
recruitment of memory T cells to an inflammatory site, independent of their antigen specificity. Additionally, increased responses
to enteric bacteria and the presence of αEβ7 T cells in synovial fluid may reflect accumulation of gut associated T cells
in the synovial compartment, even in the absence of an elevated acute phase response. This is the first report of an association
between the acute phase response and the T cell population recruited to an inflammatory site. 相似文献
10.
Mitochondria-to-nucleus stress signaling induces phenotypic changes, tumor progression and cell invasion 总被引:10,自引:0,他引:10
Amuthan G Biswas G Zhang SY Klein-Szanto A Vijayasarathy C Avadhani NG 《The EMBO journal》2001,20(8):1910-1920
Recently we showed that partial depletion of mitochondrial DNA (genetic stress) or treatment with mitochondrial-specific inhibitors (metabolic stress) induced a stress signaling that was associated with increased cytoplasmic-free Ca(2+) [Ca(2+)](c). In the present study we show that the mitochondria-to-nucleus stress signaling induces invasive phenotypes in otherwise non-invasive C2C12 myoblasts and human pulmonary carcinoma A549 cells. Tumor-specific markers cathepsin L and transforming growth factor beta (TGFbeta) are overexpressed in cells subjected to mitochondrial genetic as well as metabolic stress. C2C12 myoblasts subjected to stress showed 4- to 6-fold higher invasion through reconstituted Matrigel membrane as well as rat tracheal xenotransplants in Scid mice. Activation of Ca(2+)-dependent protein kinase C (PKC) under both genetic and metabolic stress conditions was associated with increased cathepsin L gene expression, which contributes to increased invasive property of cells. Reverted cells with approximately 70% of control cell mtDNA exhibited marker mRNA contents, cell morphology and invasive property closer to control cells. These results provide insights into a new pathway by which mitochondrial DNA and membrane damage can contribute to tumor progression and metastasis. 相似文献