全文获取类型
收费全文 | 151篇 |
免费 | 62篇 |
出版年
2021年 | 1篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2016年 | 1篇 |
2015年 | 3篇 |
2014年 | 6篇 |
2013年 | 4篇 |
2012年 | 4篇 |
2011年 | 3篇 |
2010年 | 3篇 |
2009年 | 4篇 |
2008年 | 5篇 |
2007年 | 4篇 |
2006年 | 4篇 |
2005年 | 7篇 |
2004年 | 5篇 |
2003年 | 5篇 |
2002年 | 4篇 |
2001年 | 4篇 |
2000年 | 7篇 |
1999年 | 7篇 |
1998年 | 2篇 |
1997年 | 1篇 |
1996年 | 4篇 |
1995年 | 2篇 |
1994年 | 8篇 |
1992年 | 7篇 |
1991年 | 5篇 |
1990年 | 8篇 |
1989年 | 6篇 |
1988年 | 10篇 |
1987年 | 7篇 |
1986年 | 5篇 |
1985年 | 7篇 |
1984年 | 6篇 |
1983年 | 7篇 |
1982年 | 6篇 |
1981年 | 1篇 |
1980年 | 5篇 |
1979年 | 7篇 |
1978年 | 7篇 |
1977年 | 6篇 |
1976年 | 4篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1971年 | 3篇 |
1968年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有213条查询结果,搜索用时 31 毫秒
111.
CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders 下载免费PDF全文
Brancati F Barrano G Silhavy JL Marsh SE Travaglini L Bielas SL Amorini M Zablocka D Kayserili H Al-Gazali L Bertini E Boltshauser E D'Hooghe M Fazzi E Fenerci EY Hennekam RC Kiss A Lees MM Marco E Phadke SR Rigoli L Romano S Salpietro CD Sherr EH Signorini S Stromme P Stuart B Sztriha L Viskochil DH Yuksel A Dallapiccola B;International JSRD Study Group Valente EM Gleeson JG 《American journal of human genetics》2007,81(1):104-113
Joubert syndrome–related disorders (JSRDs) are a group of clinically and genetically heterogeneous conditions that share a midbrain-hindbrain malformation, the molar tooth sign (MTS) visible on brain imaging, with variable neurological, ocular, and renal manifestations. Mutations in the CEP290 gene were recently identified in families with the MTS-related neurological features, many of which showed oculo-renal involvement typical of Senior-Löken syndrome (JSRD-SLS phenotype). Here, we performed comprehensive CEP290-mutation analysis on two nonoverlapping cohorts of JSRD-affected patients with a proven MTS. We identified mutations in 19 of 44 patients with JSRD-SLS. The second cohort consisted of 84 patients representing the spectrum of other JSRD subtypes, with mutations identified in only two patients. The data suggest that CEP290 mutations are frequently encountered and are largely specific to the JSRD-SLS subtype. One patient with mutation displayed complete situs inversus, confirming the clinical and genetic overlap between JSRDs and other ciliopathies. 相似文献
112.
Principles of tumor suppression 总被引:45,自引:0,他引:45
Molecular genetic studies of familial cancer syndromes identified and defined the recessive nature of tumor suppressor genes and resolved the paradox of why tumors arising in such families exhibited an autosomally dominant pattern of inheritance. Subsequent characterization of tumor suppressor proteins revealed their widespread involvement in sporadic cancers and pinpointed key mechanisms that protect animals against tumor development. We now recognize that tumor suppressor genes regulate diverse cellular activities, including cell cycle checkpoint responses, detection and repair of DNA damage, protein ubiquitination and degradation, mitogenic signaling, cell specification, differentiation and migration, and tumor angiogenesis. Their study has become a centerpiece of contemporary cancer research. 相似文献
113.
Evolution of the WANCY region in amniote mitochondrial DNA 总被引:7,自引:1,他引:6
In most vertebrate mitochondrial genomes, the site for initiation of
light-strand replication, OL, is found within a cluster of five transfer
RNA (tRNA) genes (tRNA(Trp), tRNA(Ala), tRNA(Asn), tRNA(Cys), and
tRNA(Tyr)). This region and part of the adjacent cytochrome c oxydase
subunit I (COI) gene were sequenced for two crocodilian, two turtle, and
one snake species and for Sphenodon punctatus; part of the adjacent
nicotinamide adenine dinucleotide dehydrogenase subunit 2 (ND2) gene was
also sequenced for the crocodilian and turtle species. All had the typical
vertebrate gene order. The turtles and the snake have a lengthy noncoding
sequence between the tRNA(Asn) and tRNA(Cys) genes that we assumed to be
homologous to the mammalian OL. The crocodilians and Sphenodon lack such a
sequence, a condition they share with birds. Most proposed phylogenies for
the amniotes require that OL at this position was lost at least twice
during their diversification or was evolved independently more than once.
Within the five tRNA genes, frequencies of substitutions are much higher in
loops than in stems. Many loops vary dramatically in size among the
species; in the most extreme case, the D-arm of the Sphenodon tRNA(Cys) is
a "D-arm replacement" loop of seven nucleotides. Frequency of transitions
in stems is relatively uniform across tRNAs, but frequency of transversions
varies greatly. Mismatches in stems are infrequent, and their relative
frequency in a specific tRNA is unrelated to the frequency of substitution
in the corresponding gene. Several features of mammalian mitochondrial
tRNAs are conserved in WANCY tRNAs throughout amniotes. The inferred
initiation codon for COI is GTG in crocodilians, turtles, and the snake, a
condition they share with fishes, certain amphibians, and birds. TTG
appears to be the initiation codon for COI in Sphenodon; if correct, this
would be a novel initiation codon for vertebrate mitochondrial DNA.
Phylogenetic analyses of the inferred amino acid sequences of ND2 and COI
support the sister-group relationship of birds and crocodilians and suggest
that mammals are an early derived lineage within the amniotes.
相似文献
114.
Early pre-B-cell transformation induced by the v-fms oncogene in long-term mouse bone marrow cultures. 总被引:3,自引:3,他引:0 下载免费PDF全文
Murine long-term bone marrow cultures that support B-lymphoid-cell development were infected with a helper-free retrovirus containing the v-fms oncogene. Infection of B-lymphoid cultures resulted in the rapid clonal outgrowth of early pre-B cells, which grew to high cell densities on stromal cell feeder layers, expressed v-fms-coded glycoproteins, and underwent immunoglobulin heavy-chain gene rearrangements. Late-passage cultures gave rise to factor-independent variants that proliferated in the absence of feeder layers, developed resistance to hydrocortisone, and became tumorigenic in syngeneic mice. The v-fms oncogene therefore recapitulates known effects of the v-abl and bcr-abl oncogenes on B-lineage cells. The ability of v-fms to induce transformation of early pre-B cells in vitro underscores the capacity of oncogenic mutants of the colony-stimulating factor-1 receptor to function outside the mononuclear phagocyte lineage. 相似文献
115.
Ligand-induced tyrosine kinase activity of the colony-stimulating factor 1 receptor in a murine macrophage cell line. 总被引:32,自引:17,他引:15 下载免费PDF全文
Metabolic labeling of simian virus 40-immortalized murine macrophages with 32Pi and immunoblotting with antibodies to phosphotyrosine demonstrated that the c-fms proto-oncogene product (colony-stimulating factor 1 [CSF-1] receptor) was phosphorylated on tyrosine in vivo and rapidly degraded in response to CSF-1. Stimulation of the CSF-1 receptor also induced immediate phosphorylation of several other cellular proteins on tyrosine. By contrast, the mature cell surface glycoprotein encoded by the v-fms oncogene was phosphorylated on tyrosine in the absence of CSF-1, suggesting that it functions as a ligand-independent kinase. 相似文献
116.
Trophic interactions within pelagic microbial communities: Indications of feedback regulation of carbon flow 总被引:4,自引:3,他引:1
Future considerations of carbon-energy flows within pelagic food webs should include internal, biotic feedback controls, in
addition to abiotic forcing functions, in the regulation of these flows. Over the past two decades, research on microbial
communities of pelagic ecosystems has yielded data suggestive of cybernetic-like regulation operating within these communities.
As presently conceived, phagotrophic protozoa have a pivotal role in such regulation as a consequence of their rapid growth,
grazing, and nutrient regenerative capabilities. Feedback controls within microbial food webs may have significant effects
on distal portions of pelagic ecosystems, including the fate of organic detritus and metazoan production. 相似文献
117.
A point mutation in the extracellular domain of the human CSF-1 receptor (c-fms proto-oncogene product) activates its transforming potential 总被引:46,自引:0,他引:46
A human CSF-1 receptor containing an "activating" mutation in its extracellular domain (serine for leucine 301) induced morphologic transformation, anchorage-independent growth, and tumorigenicity in mouse NIH 3T3 cells. A second regulatory mutation within the receptor's intracytoplasmic carboxy-terminal tail (phenylalanine for tyrosine 969) augmented transforming efficiency but was itself insufficient to induce transformation. Like the v-fms oncogene product, receptors bearing the activating mutation retained high-affinity binding sites for CSF-1 but were retarded in transport to the cell surface and were phosphorylated on tyrosine in the absence of ligand. Although the activating mutation does not affect the CSF-1 binding site in the receptor extracellular domain, it must induce a conformational change that mimics the effect of ligand binding, resulting in CSF-1-independent signals for cell growth. 相似文献
118.
Colony-stimulating factor-1 receptor (c-fms) 总被引:2,自引:0,他引:2
The macrophage colony-stimulating factor, CSF-1 (M-CSF), is a homodimeric glycoprotein required for the lineage-specific growth of cells of the mononuclear phagocyte series. Apart from its role in stimulating the proliferation of bone marrow-derived precursors of monocytes and macrophages, CSF-1 acts as a survival factor and primes mature macrophages to carry out differentiated functions. Each of the actions of CSF-1 are mediated through its binding to a single class of high-affinity receptors expressed on monocytes, macrophages, and their committed progenitors. The CSF-1 receptor (CSF-1R) is encoded by the c-fms proto-oncogene, and is one of a family of growth factor receptors that exhibits an intrinsic tyrosine-specific protein kinase activity. Transduction of c-fms sequences as a viral oncogene (v-fms) in the McDonough (SM) and HZ-5 strains of feline sarcoma virus has resulted in alterations in receptor coding sequences that affect its activity as a tyrosine kinase and provide persistent signals for cell growth in the absence of its ligand. The genetic alterations in the c-fms gene that unmask its latent transforming potential abrogate its lineage-specific activity and enable v-fms to transform a variety of cells that do not normally express CSF-1 receptors. 相似文献
119.
Perseus I Missirlis Carri-Lyn R Mead Stefanie L Butland BF Francis Ouellette Rebecca S Devon Blair R Leavitt Robert A Holt 《BMC bioinformatics》2005,6(1):145
Background
To date, 35 human diseases, some of which also exhibit anticipation, have been associated with unstable repeats. Anticipation has been reported in a number of diseases in which repeat expansion may have a role in etiology. Despite the growing importance of unstable repeats in disease, currently no resource exists for the prioritization of repeats. Here we present Satellog, a database that catalogs all pure 1–16 repeat unit satellite repeats in the human genome along with supplementary data. Satellog analyzes each pure repeat in UniGene clusters for evidence of repeat polymorphism. 相似文献120.
Idiotype-specific Ly-1 B cell-mediated helper activity: hybridomas that produce anti-idiotype antibody and nonimmunoglobulin lymphokine(s)1 总被引:3,自引:0,他引:3
Previous work has shown that the expression of a predominant family of idiotypic determinants (NPb) in the in vitro response to the 4-hydroxy-3-nitrophenyl acetyl (NP) hapten is dependent on helper activity provided by Ly-1- and Ig-bearing B cells called BH. The ability of these BH cells to perform this idiotype-specific, genetically controlled helper function is related to the NPb idiotype specificity of their cell surface receptors. However, the means by which BH cells communicate with and stimulate NPb idiotypic B cell subsets is unknown. In this paper, an Ly-1- and immunoglobulin-bearing B helper cell hybridoma is described. Supernatants from the hybridoma or its subclones were shown to specifically help the response of NPb idiotypic PFC to NP-Ficoll when added to responder cell cultures depleted of Thy-1 and Ly-1 regulatory cell populations. Under these experimental conditions hybridoma supernatants functioned in much the same fashion as populations of Ly-1- and Ig-bearing BH helper populations described previously. NPb idiotype-specific helper activity was mediated by two separable activities elaborated by the hybridoma, an anti-NPb idiotype antibody and a non-Ig (lymphokine) activity. It was shown that both the Ig and the lymphokine components were required for helper activity. Kinetics experiments showed that the anti-idiotype antibody must be added early in the response to NP-Ficoll, whereas the lymphokine fraction could be added at least as late as day 3 of a 4-day culture in order to observe NPb idiotype-specific help. The data suggest that Ly-1 B cell hybridomas may affect the responsiveness of B cell subsets initially by interaction of anti-idiotype antibody with NPb idiotypic B cell surface receptors, followed by growth or maturation signals mediated by non-Ig lymphokine(s). The possibility that the helper activity of these Ly-1 B cell hybridomas represents the combined effects of an idiotype-specific network system and nonspecific growth or maturation factor activity in direct B cell-B cell interactions is discussed. 相似文献