全文获取类型
收费全文 | 715篇 |
免费 | 148篇 |
国内免费 | 1篇 |
出版年
2021年 | 9篇 |
2018年 | 8篇 |
2016年 | 14篇 |
2015年 | 18篇 |
2014年 | 22篇 |
2013年 | 25篇 |
2012年 | 34篇 |
2011年 | 22篇 |
2010年 | 24篇 |
2009年 | 18篇 |
2008年 | 15篇 |
2007年 | 19篇 |
2006年 | 16篇 |
2005年 | 13篇 |
2004年 | 15篇 |
2003年 | 14篇 |
2002年 | 15篇 |
2001年 | 24篇 |
2000年 | 18篇 |
1999年 | 24篇 |
1998年 | 25篇 |
1997年 | 21篇 |
1996年 | 13篇 |
1995年 | 15篇 |
1994年 | 10篇 |
1993年 | 12篇 |
1992年 | 17篇 |
1991年 | 21篇 |
1990年 | 21篇 |
1989年 | 17篇 |
1988年 | 18篇 |
1987年 | 10篇 |
1986年 | 16篇 |
1985年 | 16篇 |
1984年 | 11篇 |
1983年 | 15篇 |
1982年 | 13篇 |
1981年 | 13篇 |
1980年 | 10篇 |
1979年 | 13篇 |
1978年 | 14篇 |
1977年 | 24篇 |
1976年 | 20篇 |
1975年 | 14篇 |
1974年 | 9篇 |
1973年 | 15篇 |
1972年 | 13篇 |
1971年 | 9篇 |
1968年 | 13篇 |
1966年 | 11篇 |
排序方式: 共有864条查询结果,搜索用时 509 毫秒
171.
Role of diacylglycerol-regulated protein kinase C isotypes in growth factor activation of the Raf-1 protein kinase. 总被引:14,自引:4,他引:10
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
H Cai U Smola V Wixler I Eisenmann-Tappe M T Diaz-Meco J Moscat U Rapp G M Cooper 《Molecular and cellular biology》1997,17(2):732-741
The Raf protein kinases function downstream of Ras guanine nucleotide-binding proteins to transduce intracellular signals from growth factor receptors. Interaction with Ras recruits Raf to the plasma membrane, but the subsequent mechanism of Raf activation has not been established. Previous studies implicated hydrolysis of phosphatidylcholine (PC) in Raf activation; therefore, we investigated the role of the epsilon isotype of protein kinase C (PKC), which is stimulated by PC-derived diacylglycerol, as a Raf activator. A dominant negative mutant of PKC epsilon inhibited both proliferation of NIH 3T3 cells and activation of Raf in COS cells. Conversely, overexpression of active PKC epsilon stimulated Raf kinase activity in COS cells and overcame the inhibitory effects of dominant negative Ras in NIH 3T3 cells. PKC epsilon also stimulated Raf kinase in baculovirus-infected Spodoptera frugiperda Sf9 cells and was able to directly activate Raf in vitro. Consistent with its previously reported activity as a Raf activator in vitro, PKC alpha functioned similarly to PKC epsilon in both NIH 3T3 and COS cell assays. In addition, constitutively active mutants of both PKC alpha and PKC epsilon overcame the inhibitory effects of dominant negative mutants of the other PKC isotype, indicating that these diacylglycerol-regulated PKCs function as redundant activators of Raf-1 in vivo. 相似文献
172.
Houben R Troppmair J Hidalgo J Rapp UR 《Apoptosis : an international journal on programmed cell death》1997,2(1):40-46
Growth factor deprivation induced cell death of the hematopoietic cell line 32Dcl3 is widely used as a model system to study apoptotic signalling pathways. Here we show that the onset of cell death after IL-3 withdrawal can be strongly delayed by either cycloheximide or actinomycin D, indicating that de novo protein synthesis is required. Subtractive cDNA library hybridization was used to identify genes upregulated in apoptotic 32Dcl3 cells. Here we present data showing metallothionein-I (MT-I) mRNA transiently upregulated by a factor of three- to 20-fold. Increased levels of total MT-I+II protein after IL-3 withdrawal were demonstrated. An induction of MT-I RNA as well as of MT-I+II total protein was also observed in serum deprived NIH3T3 fibroblasts. Testing the effect of different inducers of apoptosis on 32Dcl3 cells we found that only IL-3 withdrawal and ethanol treatment led to an upregulation of MT-I mRNA level. Since MTs are believed to play a role in the metabolism of zinc, we tested the effect of zinc on induced cell death. When 32Dcl3 cells are treated with zinc (50-300 M) in the absence of IL-3, loss of viability as well as degradation of the cellular DNA were delayed, indicating that zinc represses apoptosis. On the other hand zinc pre-treatment induced MT expression and accelerated the onset of apoptosis. Our data, therefore, suggest that MT exerts a proapoptotic function. 相似文献
173.
Sea urchin Hox genes: insights into the ancestral Hox cluster 总被引:3,自引:0,他引:3
We describe the Hox cluster in the radially symmetric sea urchin and
compare our findings to what is known from clusters in bilaterally
symmetric animals. Several Hox genes from the direct-developing sea urchin
Heliocidaris erythrogramma are described. CHEF gel analysis shows that the
Hox genes are clustered on a < or = 300 kilobase (kb) fragment of DNA,
and only a single cluster is present, as in lower chordates and other
nonvertebrate metazoans. Phylogenetic analyses of sea urchin, amphioxus,
Drosophila, and selected vertebrate Hox genes confirm that the H.
erythrogramma genes, and others previously cloned from other sea urchins,
belong to anterior, central, and posterior groups. Despite their radial
body plan and lack of cephalization, echinoderms retain at least one of the
anterior group Hox genes, an orthologue of Hox3. The structure of the
echinoderm Hox cluster suggests that the ancestral deuterostome had a Hox
cluster more similar to the current chordate cluster than was expected Sea
urchins have at least three Abd-B type genes, suggesting that Abd-B
expansion began before the radiation of deuterostomes.
相似文献
174.
175.
Okaama I. Dukhanina Howard Dene Alan Y. Deng Carol R. Choi Barbara Hoebee John P. Rapp 《Mammalian genome》1997,8(4):229-235
Our purposes were to develop a linkage map for rat Chromosome (Chr) 10, using chromosome-sorted DNA, and to construct congenic
strains to localize blood pressure quantitative trait loci (QTL) on Chr 10 with the map. The linkage mapping panel consisted
of three F2 populations totaling 418 rats. Thirty-two new and 29 known microsatellite markers were placed on the map, which spanned 88.9
centiMorgans (cM). The average distance between markers was 1.46 cM. No markers were separated by more than 6.8 cM. Four congenic
strains were constructed by introgressing various segments of Chr 10 from the Milan normotensive strain (MNS) onto the background
of the Dahl salt-sensitive (S) strain. A blood pressure QTL with a strong effect on blood pressure (35–42 mm Hg) when expressed
on the S background was localized to a 31-cM region between D10Mco6 and D10Mcol. The region does not include the locus for inducible nitric oxide synthase (Nos2), which had been considered to be a candidate locus for the QTL.
Received: 25 September 1996 / Accepted: 9 November 1996 相似文献
176.
Q. Y. Zhang H. Dene A. Y. Deng M. R. Garrett H. J. Jacob J. P. Rapp 《Mammalian genome》1997,8(9):636-641
The renin locus (Ren) on rat Chromosome (Chr) 13 had previously been shown to cosegregate with blood pressure in crosses involving Dahl salt-sensitive
(S) and Dahl salt-resistant (R) rats. In the present work, interval mapping of blood pressure on Chr 13 with a large F2 (S × R), n = 233, population yielded a maximum LOD = 4.2 for linkage to blood pressure, but the quantitative trait locus
(QTL) was only poorly localized to a large 35-centiMorgan (cM) segment of Chr 13. In the linkage analysis, the S-rat QTL allele
(S) was associated with higher, and the R-rat QTL allele (R) with lower blood pressure, the difference between homozygotes being about 20 mm Hg. A congenic strain was made by introgressing
the R-rat Ren allele into the recipient S strain. This congenic strain showed a 24 mm Hg reduction (P = 0.004) in blood pressure compared
with S rats for rats fed 2% NaCl diet for 24 days; this difference was confirmed by two other independent tests. Two congenic
substrains were derived from the first congenic strain with shorter R Chr 13 segments on the S background. Comparisons among
these congenic strains showed that a blood pressure QTL was in the 24-cM chromosomal segment between Syt2 and D13M1Mit108. This segment does not include the renin locus, which is thus excluded from being the gene on rat Chr 13 responsible for genetic
differences in blood pressure detected by linkage analysis.
Received: 20 December 1996 / Accepted: 7 April 1997 相似文献
177.
178.
Ekaterina Gracheva Shalaka Chitale Thomas Wilhelm Alexander Rapp Jonathan Byrne Jens Stadler Rebeca Medina M. Cristina Cardoso Holger Richly 《The Journal of cell biology》2016,213(2):185-200
Faithful DNA repair is essential to maintain genome integrity. Ultraviolet (UV) irradiation elicits both the recruitment of DNA repair factors and the deposition of histone marks such as monoubiquitylation of histone H2A at lesion sites. Here, we report how a ubiquitin E3 ligase complex specific to DNA repair is remodeled at lesion sites in the global genome nucleotide excision repair (GG-NER) pathway. Monoubiquitylation of histone H2A (H2A-ubiquitin) is catalyzed predominantly by a novel E3 ligase complex consisting of DDB2, DDB1, CUL4B, and RING1B (UV–RING1B complex) that acts early during lesion recognition. The H2A-ubiquitin binding protein ZRF1 mediates remodeling of this E3 ligase complex directly at the DNA lesion site, causing the assembly of the UV–DDB–CUL4A E3 ligase complex (DDB1–DDB2–CUL4A-RBX1). ZRF1 is an essential factor in GG-NER, and its function at damaged chromatin sites is linked to damage recognition factor XPC. Overall, the results shed light on the interplay between epigenetic and DNA repair recognition factors at DNA lesion sites. 相似文献
179.
Anna E. Rapp Ronny Bindl Stefan Recknagel Annika Erbacher Ingo Müller Hubert Schrezenmeier Christian Ehrnthaller Florian Gebhard Anita Ignatius 《PloS one》2016,11(2)
Following bone fracture, the repair process starts with an inflammatory reaction at the fracture site. Fracture healing is disturbed when the initial inflammation is increased or prolonged, whereby, a balanced inflammatory response is anticipated to be crucial for fracture healing, because it may induce down-stream responses leading to tissue repair. However, the impact of the immune response on fracture healing remains poorly understood. Here, we investigated bone healing in NOD/scid-IL2Rγcnull mice, which exhibit severe defects in innate and adaptive immunity, by biomechanical testing, histomorphometry and micro-computed tomography. We demonstrated that NOD/scid-IL2Rγcnull mice exhibited normal skeletal anatomy and a mild bone phenotype with a slightly reduced bone mass in the trabecular compartment in comparison to immunocompetent Balb/c mice. Fracture healing was impaired in immunodeficient NOD/scid-IL2Rγcnull mice. Callus bone content was unaffected during the early healing stage, whereas it was significantly reduced during the later healing period. Concomitantly, the amount of cartilage was significantly increased, indicating delayed endochondral ossification, most likely due to the decreased osteoclast activity observed in cells isolated from NOD/scid-IL2Rγcnull mice. Our results suggest that—under aseptic, uncomplicated conditions—the immediate immune response after fracture is non-essential for the initiation of bone formation. However, an intact immune system in general is important for successful bone healing, because endochondral ossification is delayed in immunodeficient NOD/scid-IL2Rγcnull mice. 相似文献
180.
Transformation of murine bone marrow cells with combined v-raf-v-myc oncogenes yields clonally related mature B cells and macrophages. 总被引:5,自引:1,他引:4
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
M Principato J L Cleveland U R Rapp K L Holmes J H Pierce H C Morse rd S P Klinken 《Molecular and cellular biology》1990,10(7):3562-3568
Murine bone marrow cells infected with replication-defective retroviruses containing v-raf alone or v-myc alone yielded transformed pre-B cell lines, while a retroviral construct containing both v-raf and v-myc oncogenes produced clonally related populations of mature B cells and mature macrophages. The genealogy of these transformants demonstrates that mature myeloid cells were derived from cells with apparent B-lineage commitment and functional immunoglobulin rearrangements. This system should facilitate studies of developmental relationships in hematopoietic differentiation and analysis of lineage determination. 相似文献