全文获取类型
收费全文 | 1132篇 |
免费 | 153篇 |
专业分类
1285篇 |
出版年
2023年 | 12篇 |
2022年 | 30篇 |
2021年 | 60篇 |
2020年 | 24篇 |
2019年 | 26篇 |
2018年 | 38篇 |
2017年 | 35篇 |
2016年 | 54篇 |
2015年 | 101篇 |
2014年 | 85篇 |
2013年 | 96篇 |
2012年 | 116篇 |
2011年 | 104篇 |
2010年 | 45篇 |
2009年 | 35篇 |
2008年 | 40篇 |
2007年 | 59篇 |
2006年 | 50篇 |
2005年 | 34篇 |
2004年 | 31篇 |
2003年 | 24篇 |
2002年 | 27篇 |
2001年 | 13篇 |
2000年 | 14篇 |
1999年 | 9篇 |
1997年 | 6篇 |
1996年 | 8篇 |
1995年 | 4篇 |
1994年 | 7篇 |
1993年 | 5篇 |
1992年 | 5篇 |
1991年 | 5篇 |
1989年 | 6篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1974年 | 4篇 |
1972年 | 2篇 |
1969年 | 2篇 |
1931年 | 2篇 |
排序方式: 共有1285条查询结果,搜索用时 15 毫秒
1.
M Janowski L Baugnet-Mahiec J Merregaert L de Saint-Georges A Sassen J N Ihle J R Maisin 《Comptes rendus des séances de la Société de biologie et de ses filiales》1980,174(5):832-839
Two distinct rat propagates of a radiation leukemia virus (RadLV-Rs) from the C57BL mouse respectively induced characteristic leukemogenic effects. These were found to be related with the infection titers of the isolates, but not with either their antigenic specificities or their viral and proviral genome sequences. 相似文献
2.
3.
Hematopoietic cell phosphatase (Hcph) was identified by amplification of conserved protein tyrosine phosphatase sequences from a myeloid cell line and is predominantly expressed in hematopoietic cells. Hcph is unique in containing two, tandemly repeated, src-homology 2 domains in the amino terminal region of the phosphatase. Using a genomic probe in interspecific backcross analysis, the murine Hcph gene maps to mouse Chromosome 6 and is tightly linked to the Tnfr-2 and Ly-4 genes. 相似文献
4.
J R Keller Y Weinstein M Hursey J N Ihle 《Journal of immunology (Baltimore, Md. : 1950)》1985,135(3):1864-1871
The ability of interleukin 2 (IL 2), interleukin 3 (IL 3), and granulocyte/macrophage colony-stimulating factor (GM-CSF) to induce the proliferation of cells from thymus, spleen, or bone marrow was examined and compared with their ability to induce expression of the enzyme 20-alpha-hydroxysteroid dehydrogenase (20 alpha SDH). In the thymus, the peanut agglutinin agglutinated cells (PNA+) lacked 20 alpha SDH and showed no detectable response to IL 2, IL 3, or GM-CSF in either proliferation or induction of 20 alpha SDH. In contrast, the PNA nonagglutinated (PNA-) subpopulation expressed 20 alpha SDH and proliferated in response to Con A and/or IL 2. The responding cells that could be expanded in vitro with IL 2 expressed high levels of 20 alpha SDH. Neither IL 3 nor GM-CSF in the presence or absence of Con A had a demonstrable effect on the PNA- population. In cultures of bone marrow cells, both IL 3 and GM-CSF induced proliferation, whereas IL 2 had no effect on proliferation in the presence or absence of Con A. Thy-1-depleted bone marrow cells, expanded in tissue culture with IL3, contained cells that co-expressed Thy-1 and 20 alpha SDH. In contrast, cells proliferating in vitro to GM-CSF did not expressed Thy-1 or 20 alpha SDH. In cultures of normal splenic lymphocytes, two populations of cells capable of expressing 20 alpha SDH were detected. One population could be expanded in vitro with IL 2 and Con A, whereas the second was responsive to IL 3. In spleens from athymic mice, only the latter cells were detected. These results demonstrate that IL 3 and IL 2 responsiveness distinguishes two populations of 20 alpha SDH cells. The relevance of these observations to the possible relationship of IL 3 and IL 2 in T cell differentiation is discussed. 相似文献
5.
6.
Activation of the c-H-ras proto-oncogene by retrovirus insertion and chromosomal rearrangement in a Moloney leukemia virus-induced T-cell leukemia. 总被引:4,自引:2,他引:2 下载免费PDF全文
J N Ihle B Smith-White B Sisson D Parker D G Blair A Schultz C Kozak R D Lunsford D Askew Y Weinstein et al. 《Journal of virology》1989,63(7):2959-2966
A rearrangement of the c-H-ras locus was detected in a T-cell line (DA-2) established from a Moloney leukemia virus-induced tumor. This rearrangement was associated with the high-level expression of H-ras RNA and the H-ras gene product, p21. DNA from DA-2 cells transformed fibroblasts in DNA transfection experiments, and the transformed fibroblasts contained the rearranged H-ras locus. The rearrangement involved one allele and was present in tissue from the primary tumor from which the cell line was isolated. Cloning and sequencing of the rearranged allele and comparison with the normal allele demonstrated that the rearrangement was complex and probably resulted from the integration of a retrovirus in the H-ras locus between a 5' noncoding exon and the first coding exon and a subsequent homologous recombination between this provirus and another newly acquired provirus also located on chromosome 7. These events resulted in the translocation of the coding exons of the H-ras locus away from the 5' noncoding exon region to a new genomic site on chromosome 7. Sequencing of the coding regions of the gene failed to detect mutations in the 12th, 13th, 59th, or 61st codons. The possible reasons for the complexity of the rearrangement and the significance of the activation of the H-ras locus to T-cell transformation are discussed. 相似文献
7.
JAK2 associates with the beta c chain of the receptor for granulocyte-macrophage colony-stimulating factor, and its activation requires the membrane-proximal region. 总被引:32,自引:10,他引:22 下载免费PDF全文
F W Quelle N Sato B A Witthuhn R C Inhorn M Eder A Miyajima J D Griffin J N Ihle 《Molecular and cellular biology》1994,14(7):4335-4341
The high-affinity receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) consists of a unique alpha chain and a beta c subunit that is shared with the receptors for interleukin-3 (IL-3) and IL-5. Two regions of the beta c chain have been defined; these include a membrane-proximal region of the cytoplasmic domain that is required for mitogenesis and a membrane-distal region that is required for activation of Ras, Raf-1, mitogen-activated protein kinase, and S6 kinase. Recent studies have implicated the cytoplasmic protein tyrosine kinase JAK2 in signalling through a number of the cytokine receptors, including the IL-3 and erythropoietin receptors. In the studies described here, we demonstrate that GM-CSF stimulation of cells induces the tyrosine phosphorylation of JAK2 and activates its in vitro kinase activity. Mutational analysis of the beta c chain demonstrates that only the membrane-proximal 62 amino acids of the cytosolic domain are required for JAK2 activation. Thus, JAK2 activation is correlated with induction of mitogenesis but does not, alone, activate the Ras pathway. Carboxyl truncations of the alpha chain, which inactivate the receptor for mitogenesis, are unable to mediate GM-CSF-induced JAK2 activation. Using baculovirus-expressed proteins, we further demonstrate that JAK2 physically associates with the beta c chain but not with the alpha chain. Together, the results further support the hypothesis that the JAK family of kinase are critical to coupling cytokine binding to tyrosine phosphorylation and ultimately mitogenesis. 相似文献
8.
Inactivation of erythropoietin receptor function by point mutations in a region having homology with other cytokine receptors. 总被引:21,自引:11,他引:10 下载免费PDF全文
The cytoplasmic domain of the erythropoietin receptor (EpoR) contains a region, proximal to the transmembrane domain, that is essential for function and has homology with other members of the cytokine receptor family. To explore the functional significance of this region and to identify critical residues, we introduced several amino acid substitutions and examined their effects on erythropoietin-induced mitogenesis, tyrosine phosphorylation, and expression of immediate-early (c-fos, c-myc, and egr-1) and early (ornithine decarboxylase and T-cell receptor gamma) genes in interleukin-3-dependent cell lines. Amino acid substitution of W-282, which is strictly conserved at the middle portion of the homology region, completely abolished all the functions of the EpoR. Point mutation at L-306 or E-307, both of which are in a conserved LEVL motif, drastically impaired the function of the receptor in all assays. Other point mutations, introduced into less conserved amino acid residues, did not significantly impair the function of the receptor. These results demonstrate that conserved amino acid residues in this domain of the EpoR are required for mitogenesis, stimulation of tyrosine phosphorylation, and induction of immediate-early and early genes. 相似文献
9.
The genes encoding the peripheral cannabinoid receptor and alpha-L-fucosidase are located near a newly identified common virus integration site, Evi11. 总被引:2,自引:0,他引:2 下载免费PDF全文
P J Valk S Hol Y Vankan J N Ihle D Askew N A Jenkins D J Gilbert N G Copeland N J de Both B Lwenberg R Delwel 《Journal of virology》1997,71(9):6796-6804
A new common region of virus integration, Evi11, has been identified in two retrovirally induced murine myeloid leukemia cell lines, NFS107 and NFS78. By interspecific backcross analysis, it was shown that Evi11 is located at the distal end of mouse chromosome 4, in a region that shows homology with human 1p36. The genes encoding the peripheral cannabinoid receptor (Cnr2) and alpha-L-fucosidase (Fuca1) were identified near the integration site by using a novel exon trapping system. Cnr2 is suggested to be the target gene for viral interference in Evi11, since proviruses are integrated in the first intron of Cnr2 and retroviral integrations alter mRNA expression of Cnr2 in NFS107 and NFS78. In addition, proviral integrations were demonstrated within the 3' untranslated region of Cnr2 in five independent newly derived CasBrM-MuLV (mouse murine leukemia virus) tumors, CSL13, CSL14, CSL16, CSL27, and CSL97. The Cnr2 gene encodes a seven-transmembrane G-protein-coupled receptor which is normally expressed in hematopoietic tissues. Our data suggest that the peripheral cannabinoid receptor gene might be involved in leukemogenesis as a result of aberrant expression of Cnr2 due to retroviral integration in Evi11. 相似文献
10.
Resistance of cultures of normal T cells to infection with murine type C viruses. 总被引:5,自引:3,他引:2 下载免费PDF全文
Long-term continuous cultures of normal T cells were established from C57BL/6 and BALB/c mice by using conditioned medium from concanavalin A-stimulated lymphocytes. The ability of various murine type C viruses to infect these normal T cell cultures was examined and compared with their ability to infect transformed T cells. All of the viruses examined, including a thymotropic radiation leukemia virus, were unable to infect and replicate in normal T cells but readily did so in transformed T cells. 相似文献