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111.
Wang J Iwasaki H Krivtsov A Febbo PG Thorner AR Ernst P Anastasiadou E Kutok JL Kogan SC Zinkel SS Fisher JK Hess JL Golub TR Armstrong SA Akashi K Korsmeyer SJ 《The EMBO journal》2005,24(2):368-381
Chromosomal translocations that fuse the mixed lineage leukemia (MLL) gene with multiple partners typify acute leukemias of infancy as well as therapy-related leukemias. We utilized a conditional knockin strategy to bypass the embryonic lethality caused by MLL-CBP expression and to assess the immediate effects of induced MLL-CBP expression on hematopoiesis. Within days of activating MLL-CBP, the fusion protein selectively expanded granulocyte/macrophage progenitors (GMP) and enhanced their self-renewal/proliferation. MLL-CBP altered the gene expression program of GMP, upregulating a subset of genes including Hox a9. Inhibition of Hox a9 expression by RNA interference demonstrated that MLL-CBP required Hox a9 for its enhanced cell expansion. Following exposure to sublethal gamma-irradiation or N-ethyl-N-nitrosourea (ENU), MLL-CBP mice developed myelomonocytic hyperplasia and progressed to fatal myeloproliferative disorders. These represented the spectrum of therapy-induced acute myelomonocytic leukemia/chronic myelomonocytic leukemia/myelodysplastic/myeloproliferative disorder similar to that seen in humans possessing the t(11;16). This model of MLL-CBP therapy-related myeloproliferative disease demonstrates the selectivity of this MLL fusion for GMP cells and its ability to initiate leukemogenesis in conjunction with cooperating mutations. 相似文献
112.
Epstein-Barr-virus-encoded LMP2A induces primary epithelial cell migration and invasion: possible role in nasopharyngeal carcinoma metastasis 总被引:5,自引:0,他引:5 下载免费PDF全文
Pegtel DM Subramanian A Sheen TS Tsai CH Golub TR Thorley-Lawson DA 《Journal of virology》2005,79(24):15430-15442
Nonkeratinizing nasopharyngeal carcinomas (NPC) are >95% associated with the expression of the Epstein-Barr virus (EBV) LMP2A latent protein. However, the role of EBV, in particular, LMP2A, in tumor progression is not well understood. Using Affymetrix chips and a pattern-matching computational technique (neighborhood analysis), we show that the level of LMP2A expression in NPC biopsy samples correlates with that of a cellular protein, integrin-alpha-6 (ITGalpha6), that is associated with cellular migration in vitro and metastasis in vivo. We have recently developed a primary epithelial model from tonsil tissue to study EBV infection in epithelial cells. Here we report that LMP2A expression in primary tonsil epithelial cells causes them to become migratory and invasive, that ITGalpha6 RNA levels are up-regulated in epithelial cells expressing LMP2, and that ITGalpha6 protein levels are increased in the migrating cells. Blocking antibodies against ITGalpha6 abrogated LMP2-induced invasion through Matrigel by primary epithelial cells. Our results provide a link between LMP2A expression, ITGalpha6 expression, epithelial cell migration, and NPC metastasis and suggest that EBV infection may contribute to the high incidence of metastasis in NPC progression. 相似文献
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114.
mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways 总被引:22,自引:0,他引:22
115.
Yeang CH Ramaswamy S Tamayo P Mukherjee S Rifkin RM Angelo M Reich M Lander E Mesirov J Golub T 《Bioinformatics (Oxford, England)》2001,17(Z1):S316-S322
Using gene expression data to classify tumor types is a very promising tool in cancer diagnosis. Previous works show several pairs of tumor types can be successfully distinguished by their gene expression patterns (Golub et al. 1999, Ben-Dor et al. 2000, Alizadeh et al. 2000). However, the simultaneous classification across a heterogeneous set of tumor types has not been well studied yet. We obtained 190 samples from 14 tumor classes and generated a combined expression dataset containing 16063 genes for each of those samples. We performed multi-class classification by combining the outputs of binary classifiers. Three binary classifiers (k-nearest neighbors, weighted voting, and support vector machines) were applied in conjunction with three combination scenarios (one-vs-all, all-pairs, hierarchical partitioning). We achieved the best cross validation error rate of 18.75% and the best test error rate of 21.74% by using the one-vs-all support vector machine algorithm. The results demonstrate the feasibility of performing clinically useful classification from samples of multiple tumor types. 相似文献
116.
V S Kiktenko A P Shirkovskaia G I Ezhov V P Golub 《Zhurnal mikrobiologii, epidemiologii, i immunobiologii》1977,(1):70-74
The authors considered different views of investigators on the diagnostic antibody titre level in the microagglutination test (MAT) in leptospirosis of man and animals. Some of them took into consideration MAT in low titres (1:10-1:20), and others - in high only (1:400, 1:1000), which gave no possibility to assess the state of leptospirosis morbidity. The authors suggest that the assessment of the level of the titres in single and repeated studies should be approached differentially. In single examination 1:100 and over should be considered as a positive MAT titre for man, 1:200 and over - for cattle, 1:20 and over - for swine, and 1:20 and over for murine rodents. In repeated investigations any level of the titre in case of its dynamics should be taken into consideration. 相似文献
117.
Summary A total of 739 sera from cancer patients, noncancer patients and normal donors were analyzed for anticomplementary (AC) activity by the complement consumption method. The results were correlated with clinical stage and tumor burden. The incidence of AC activity in cancer and noncancer patients' sera was 53% (233/439) and 67% (100/150), respectively, as against 14% (20/140) in normal donors' sera. Among cancer patients, this incidence was lowest (42%) for melanoma sera and highest (65%) for lung carcinoma sera. With the exception of sarcoma sera, the incidence of AC activity did not differ significantly with clinical Stages I, II, or III. Sera from Stages II and III sarcoma patients had a significantly higher incidence of AC activity (73% and 63%, respectively) than Stage I (38%). There appeared to be a higher incidence of AC activity in sera of cancer patients with 1–100 g tumor burden than in those from patients with tumors greater than 100 g or less than 1 g. Follow-up of cancer patients with no evidence of disease or minimal tumor burden revealed that 42% (18/43) whose sera were AC-positive had tumor recurrence within 3 months and 90% (57/63) whose sera were AC-negative had no detectable tumor recurrence up to at least 6 months after the serum analysis. 相似文献
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119.
On the effects of cyanide on phenoxazinone synthetase 总被引:1,自引:0,他引:1
120.
Anjali Sharma Donald R. Hoover Qiuhu Shi Deborah Gustafson Michael W. Plankey Ronald C. Hershow Phyllis C. Tien Elizabeth T. Golub Kathryn Anastos 《PloS one》2015,10(12)