全文获取类型
收费全文 | 158篇 |
免费 | 25篇 |
出版年
2022年 | 1篇 |
2021年 | 3篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2017年 | 2篇 |
2016年 | 4篇 |
2015年 | 6篇 |
2014年 | 6篇 |
2013年 | 13篇 |
2012年 | 11篇 |
2011年 | 13篇 |
2010年 | 8篇 |
2009年 | 8篇 |
2008年 | 8篇 |
2007年 | 8篇 |
2006年 | 7篇 |
2005年 | 4篇 |
2004年 | 9篇 |
2003年 | 8篇 |
2002年 | 7篇 |
2001年 | 3篇 |
2000年 | 5篇 |
1999年 | 3篇 |
1998年 | 6篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1993年 | 1篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1972年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1924年 | 1篇 |
排序方式: 共有183条查询结果,搜索用时 15 毫秒
1.
2.
Expression of a human multidrug resistance cDNA (MDR1) in the bone marrow of transgenic mice: resistance to daunomycin-induced leukopenia. 总被引:7,自引:0,他引:7
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 Galski M Sullivan M C Willingham K V Chin M M Gottesman I Pastan G T Merlino 《Molecular and cellular biology》1989,9(10):4357-4363
The human multidrug resistance gene (MDR1) encodes a drug efflux pump glycoprotein (P-glycoprotein) responsible for resistance to multiple cytotoxic drugs. A plasmid carrying a human MDR1 cDNA under the control of a chicken beta-actin promoter was used to generate transgenic mice in which the transgene was mainly expressed in bone marrow and spleen. Immunofluorescence localization studies showed that P-glycoprotein was present on bone marrow cells. Furthermore, leukocyte counts of the transgenic mice treated with daunomycin did not fall, indicating that their bone marrow was resistant to the cytotoxic effect of the drug. Since bone marrow suppression is a major limitation to chemotherapy, these transgenic mice should serve as a model to determine whether higher doses of drugs can cure previously unresponsive cancers. 相似文献
3.
4.
Synthesis of epidermal growth factor (EGF) receptor in vitro using SP6 RNA polymerase-transcribed template mRNA 总被引:2,自引:0,他引:2
A J Clark L Beguinot S Ishii D P Ma B A Roe G T Merlino I Pastan 《Biochimica et biophysica acta》1986,867(4):244-251
The epidermal growth factor (EGF) receptor plays a key role in the control cellular proliferation, and its homology to the avian erythroblastosis virus erb B oncogene implicates its involvement in cellular transformation. The establishment of a correlation between the various structural domains of the EGF receptor and their functional counterparts would greatly advance our understanding of these processes. To this end, we have constructed an expression vector containing the SP6 viral promoter and an adjacent cDNA fragment encoding the full-length EGF receptor. Upon addition of SP6 RNA polymerase, this DNA is capable of generating large amounts of EGF receptor mRNA; this RNA can then be translated in vitro into immunoprecipitable EGF receptor protein. The translational efficiency of this EGF receptor RNA was found to be relatively low: approx. 100-fold lower than globin RNA synthesized using SP6 RNA polymerase. Use of these tools should now permit the synthesis and analysis of mutated EGF receptor protein in an effort to clarify the role of this receptor in growth control. 相似文献
5.
Structure and localization of genes encoding aberrant and normal epidermal growth factor receptor RNAs from A431 human carcinoma cells. 总被引:18,自引:6,他引:12
G T Merlino S Ishii J Whang-Peng T Knutsen Y H Xu A J Clark R H Stratton R K Wilson D P Ma B A Roe et al. 《Molecular and cellular biology》1985,5(7):1722-1734
A431 cells have an amplification of the epidermal growth factor (EGF) receptor gene, the cellular homolog of the v-erb B oncogene, and overproduce an aberrant 2.9-kilobase RNA that encodes a portion of the EGF receptor. A cDNA (pE15) for the aberrant RNA was cloned, sequenced, and used to analyze genomic DNA blots from A431 and normal cells. These data indicate that the aberrant RNA is created by a gene rearrangement within chromosome 7, resulting in a fusion of the 5' portion of the EGF receptor gene to an unidentified region of genomic DNA. The unidentified sequences are amplified to about the same degree (20- to 30-fold) as the EGF receptor sequences. In situ hybridization to chromosomes from normal cells and A431 cells show that both the EGF receptor gene and the unidentified DNA are localized to the p14-p12 region of chromosome 7. By using cDNA fragments to probe DNA blots from mouse-A431 somatic cell hybrids, the rearranged receptor gene was shown to be associated with translocation chromosome M4. 相似文献
6.
7.
Targeting expression of a transforming growth factor beta 1 transgene to the pregnant mammary gland inhibits alveolar development and lactation. 总被引:14,自引:0,他引:14
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
C Jhappan A G Geiser E C Kordon D Bagheri L Hennighausen A B Roberts G H Smith G Merlino 《The EMBO journal》1993,12(5):1835-1845
Transforming growth factor-beta 1 (TGF-beta 1) possesses highly potent, diverse and often opposing cell-specific activities, and has been implicated in the regulation of a variety of physiologic and developmental processes. To determine the effects of in vivo overexpression of TGF-beta 1 on mammary gland function, transgenic mice were generated harboring a fusion gene consisting of the porcine TGF-beta 1 cDNA placed under the control of regulatory elements of the pregnancy-responsive mouse whey-acidic protein (WAP) gene. Females from two of four transgenic lines were unable to lactate due to inhibition of the formation of lobuloalveolar structures and suppression of production of endogenous milk protein. In contrast, ductal development of the mammary glands was not overtly impaired. There was a complete concordance in transgenic mice between manifestation of the lactation-deficient phenotype and expression of RNA from the WAP/TGF-beta 1 transgene, which was present at low levels in the virgin gland, but was greatly induced at mid-pregnancy. TGF-beta 1 was localized to numerous alveoli and to the periductal extracellular matrix in the mammary gland of transgenic females late in pregnancy by immunohistochemical analysis. Glands reconstituted from cultured transgenic mammary epithelial cells duplicated the inhibition of lobuloalveolar development observed in situ in the mammary glands of pregnant transgenic mice. Results from this transgenic model strongly support the hypothesis that TGF-beta 1 plays an important in vivo role in regulating the development and function of the mammary gland. 相似文献
8.
Molecular mapping of wheat. Homoeologous group 2. 总被引:21,自引:0,他引:21
J C Nelson A E Deynze M E Sorrells E Autrique Y H Lu M Merlino M Atkinson P Leroy 《Génome》1995,38(3):516-524
A molecular-marker map of bread wheat having many markers in common with other grasses in the Gramineae family is a prerequisite for molecular level genetic studies and breeding in this crop species. We have constructed restriction fragment length polymorphism maps of the A-, B-, and D-genome chromosomes of homoeologous group 2 of hexaploid wheat (Triticum aestivum L. em. Thell) using 114 F7 lines from a synthetic x bread wheat cross and clones from 11 libraries. Chromosomes 2A, 2B, and 2D comprise 57, 60, and 56 markers and each spans about 200 cM. Comparisons between chromosomes are facilitated by 26 sets of homoeoloci. Genes mapped include a heterologous abscisic acid responsive locus cloned as pBS128, the epidermal waxiness inhibitor W21, and two presumed leaf rust and stem rust resistance genes. Anomalies suggesting ancestral rearrangements in chromosome 2B are pointed out and features of wheat group 2 chromosomes that are common to barley (Hordeum vulgare L.), rice (Oryza spp.), and T. tauschii are discussed. 相似文献
9.
Using a battery of seven lectin-ferritin conjugates as probes for cell surface glycoconjugates, we have studied the pattern of plasmalemmal differentiation of cells in the embryonic rat pancreas from day 15 in utero to the early postpartum stage. Our results indicate that differentiation of plasmalemmal glycoconjugates on acinar, endocrine, and centroacinar cells is temporally correlated with development and is unique for each cell type, as indicated by lectin-ferritin binding. Specifically, (a) expression of adult cell surface saccharide phenotype can be detected on presumptive acinar cells as early as 15 d in utero, as indicated by soybean agglutinin binding, and precedes development of intracellular organelles characteristic of mature acinar cells; (b) maturation of the plasmalemma of acinar cells is reached after intracellular cytodifferentiation is completed, as indicated by appearance of Con A and fucoselectin binding sites only at day 19 of development; conversely, maturation of the endocrine cell plasmalemma is accompanied by "loss" (masking) of ricinus communis II agglutinin receptors; and (c) binding sites for fucose lectins and for soybean agglutinin are absent on endocrine and centroacinar cells at all stages examined. We conclude that acinar, centroacinar, and endocrine cells develop from a common progenitor cell(s) whose plasmalemmal carbohydrate composition resembles most closely that of the adult centroacinar cell. Finally, appearance of acinar lumina beginning at approximately 17 d in utero is accompanied by differenetiation of apical and basolateral plasmalemmal domains of epithelial cells, as indicated by enhanced binding of several lectin-ferritin conjugates to the apical plasmalemmal, a pattern that persists from this stage through adult life. 相似文献
10.
Alain Gagnon Matthew S. Miller Stacey A. Hallman Robert Bourbeau D. Ann Herring David JD. Earn Joaquín Madrenas 《PloS one》2013,8(8)
The worldwide spread of a novel influenza A (H1N1) virus in 2009 showed that influenza remains a significant health threat, even for individuals in the prime of life. This paper focuses on the unusually high young adult mortality observed during the Spanish flu pandemic of 1918. Using historical records from Canada and the U.S., we report a peak of mortality at the exact age of 28 during the pandemic and argue that this increased mortality resulted from an early life exposure to influenza during the previous Russian flu pandemic of 1889–90. We posit that in specific instances, development of immunological memory to an influenza virus strain in early life may lead to a dysregulated immune response to antigenically novel strains encountered in later life, thereby increasing the risk of death. Exposure during critical periods of development could also create holes in the T cell repertoire and impair fetal maturation in general, thereby increasing mortality from infectious diseases later in life. Knowledge of the age-pattern of susceptibility to mortality from influenza could improve crisis management during future influenza pandemics.
“The war is over – and I must go” Egon Schiele, 1890–1918.相似文献