全文获取类型
收费全文 | 234篇 |
免费 | 12篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 7篇 |
2020年 | 3篇 |
2019年 | 4篇 |
2018年 | 11篇 |
2017年 | 6篇 |
2016年 | 4篇 |
2015年 | 7篇 |
2014年 | 9篇 |
2013年 | 16篇 |
2012年 | 31篇 |
2011年 | 10篇 |
2010年 | 10篇 |
2009年 | 8篇 |
2008年 | 21篇 |
2007年 | 12篇 |
2006年 | 14篇 |
2005年 | 13篇 |
2004年 | 4篇 |
2003年 | 13篇 |
2002年 | 10篇 |
2001年 | 3篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 1篇 |
1989年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 3篇 |
1927年 | 1篇 |
排序方式: 共有246条查询结果,搜索用时 31 毫秒
61.
Khalid A Azim MK Parveen S Atta-ur-Rahman Choudhary MI 《Biochemical and biophysical research communications》2005,331(4):1528-1532
Acetylcholinesterase plays a crucial role in the metabolism of neurotransmitter, acetylcholine. Inhibition of Torpedo californica acetylcholinesterase by triterpenoidal alkaloids buxamine-B (1) and buxamine-C (2) has been studied by enzyme kinetics and molecular docking experiments. Buxamine-C (2) has been found to be 20-fold potent than buxamine-B (1) (Ki = 5.5 and 110 microM, respectively). The ligand docking experiments predicted that the cyclopentanophenanthrene skeleton of both inhibitors properly fits into the aromatic gorge of the enzyme. The C-3 and C-20 amino groups of both alkaloids mimic the well-known bis-quaternary ammonium inhibitors such as decamethonium and interact with Trp84 and Trp279 residues of the enzyme, respectively. The C-3 amino group in buxamine-C (2) appears to be better positioned at the bottom of the aromatic gorge and thus seems to be crucial for the inhibitory activity of such inhibitors. 相似文献
62.
Initiation of epigenetic reprogramming of the X chromosome in somatic nuclei transplanted to a mouse oocyte 总被引:1,自引:0,他引:1
The active and inactive X chromosomes have distinct epigenetic marks in somatic nuclei, which undergo reprogramming after transplantation into oocytes. We show that, despite the disappearance of Xist RNA coating in 30 min, the epigenetic memory of the inactive X persists with the precocious appearance of histone H3 trimethylation of lysine 27 (H3-3meK27), without the expected colocalization with Eed/Ezh2. Subsequently, Xist re-appears on the original inactive X, and the silent Xist on the active X undergoes re-activation, resulting in unusual biallelic Xist RNA domains. Despite this abnormal Xist expression pattern, colocalization of H3-3meK27 and Eed is thereafter confined to a single Xist domain, which is presumably on the original inactive X. These epigenetic events differ markedly from the kinetics of preferential paternal X inactivation in normal embryos. All the epigenetic marks on the X are apparently erased in the epiblast, suggesting that the oocyte and epiblast may have distinct properties for stepwise programming of the genome. 相似文献
63.
Transient neonatal diabetes mellitus (TNDM) is a rare disease characterized by intrauterine growth retardation, dehydration, and failure to thrive due to a lack of normal insulin secretion. This disease is associated with paternal uniparental disomy or paternal duplication of chromosome 6, suggesting that the causative gene(s) for TNDM is imprinted. Recently, Gardner et al. (1999, J. Med. Genet. 36: 192–196) proposed that a candidate gene for TNDM lies within chromosome 6q24.1–q24.3. To find human imprinted genes, we performed a database search for EST sequences that mapped to this region, followed by RT-PCR analysis using monochromosomal hybrid cells with a human chromosome 6 of defined parental origin. Here we report the identification of a novel imprinted gene, HYMAI. This gene exhibits differential DNA methylation between the two parental alleles at an adjacent CpG island and is expressed only from the paternal chromosome. A previously characterized imprinted gene, ZAC/LOT1, is located 70 kb downstream of HYMAI and is also expressed only from the paternal allele. In the pancreas, both genes are moderately expressed. HYMAI and ZAC/LOT1 are therefore candidate genes involved in TNDM. Furthermore, the human chromosome 6q24 region is syntenic to mouse chromosome 10 and represents a novel imprinted domain. 相似文献
64.
Colcemid inhibits growth during early G1 in normal but not in tumorigenic lymphocytes 总被引:3,自引:0,他引:3
Mitogenically stimulated human and mouse lymphocytes enter the cell cycle (G0, G1A, G1B, S, G2+M) via a newly recognized subphase, G1'. This subphase precedes G1A and is distinct from G0. The G1' subphase is absent in immortalized and tumorigenic lymphoblastoid cell lines (LCLs) by cytofluorimetric criteria. Furthermore, colcemid inhibits transition through the G0/G1' as well as G2 phases in mitogen-stimulated lymphocytes and in LCLs. Tumorigenic LCLs are not sensitive to growth inhibition by colcemid during early G1. These observations suggest that a progressive series of changes have occurred during G0/G1' which lead to deregulation of growth control. 相似文献
65.
66.
Benjamin M. Johnson Faisal F. Y. Radwan Azim Hossain Bently P. Doonan Jessica D. Hathaway-Schrader Jason M. God Christina V. Voelkel-Johnson Narendra L. Banik Sakamuri V. Reddy Azizul Haque 《Journal of cellular biochemistry》2019,120(4):6264-6276
Though the current therapies are effective at clearing an early stage prostate cancer, they often fail to treat late-stage metastatic disease. We aimed to investigate the molecular mechanisms underlying the anticancer effects of a natural triterpenoid, ganoderic acid DM (GA-DM), on two human prostate cancer cell lines: the androgen-independent prostate carcinoma (PC-3), and androgen-sensitive prostate adenocarcinoma (LNCaP). Cell viability assay showed that GA-DM was relatively more toxic to LNCaP cells than to PC-3 cells (IC50s ranged 45-55 µM for PC-3, and 20-25 µM for LNCaP), which may have occurred due to differential expression of p53. Hoechst DNA staining confirmed detectable nuclear fragmentation in both cell lines irrespective of the p53 status. GA-DM treatment decreased Bcl-2 proteins while it upregulated apoptotic Bax and autophagic Beclin-1, Atg5, and LC-3 molecules, and caused an induction of both early and late events of apoptotic cell death. Biochemical analyses of GA-DM-treated prostate cancer cells demonstrated that caspase-3 cleavage was notable in GA-DM-treated PC-3 cells. Interestingly, GA-DM treatment altered cell cycle progression in the S phase with a significant growth arrest in the G2 checkpoint and enhanced CD4 + T cell recognition of prostate tumor cells. Mechanistic study of GA-DM-treated prostate cancer cells further demonstrated that calpain activation and endoplasmic reticulum stress contributed to cell death. These findings suggest that GA-DM is a candidate for future drug design for prostate cancer as it activates multiple pathways of cell death and immune recognition. 相似文献
67.
68.
Huma Asif Asifullah Khan Asif Iqbal Ishtiaq Ahmad Khan Berthold Heinze M. Kamran Azim 《Tree Genetics & Genomes》2013,9(3):867-877
Only a few studies to date have conducted comparative genomics in the Myrtaceae family. Here, we report the complete sequence and bioinformatics analysis of the chloroplast genome of Syzygium cumini (L.), one of the family members. The size of S. cumini cp genome was within the range of reported angiosperm chloroplast genomes. Comparison of S. cumini cpDNA sequence with previously reported partial sequences of S. cumini revealed several SNPs that resulted in non-synonymous mutations in maturase K and NADH-plastoquinone oxidoreductase subunit-5. These polymorphic characters might serve as intra-specific markers to address whether lineage sorting from polymorphic ancestry has occurred. Comparison of the S. cumini chloroplast genome with related dicots revealed an expansion in the intergenic spacer located between IRA/large single copy (LSC) border and the first gene of LSC region, driven by sequence of 54 bp. This type of variation in the intergenic regions can be utilized in the development of species-specific vectors for chloroplast genetic engineering. Several of the longer (30–40 bp) repeats were found to be conserved in other dicot species, suggesting that they might be widespread in angiosperm chloroplast genomes. 相似文献
69.
Janis Jansons James Stattel Annalisa Verri Joseph Gambino Naseema Khan Federico Focher 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):669-682
Abstract N2-(p-n-Octylphenyl)-2′-deoxyguanosine 5′-triphosphate (OctPdGTP)has been synthesized chemically. OctPdGTP inhibited DNA polymerases (pol) α, δ and ε from calf thymus, with moderate selectivity for pol α. Mechanistic studies on pol α and bacteriophage T4 DNA polymerase revealed competitive and mixed kinetics of OctPdGTP with respect to the substrate dGTP when the enzymes were assayed on activated DNA and oligo dT:poly dA, respectively. 相似文献
70.
Zhao D Amria S Hossain A Sundaram K Komlosi P Nagarkatti M Haque A 《Cellular immunology》2011,(2):392-400
The majority of melanoma cells express detectable levels of HLA class II proteins, and an increased threshold of cell surface class II is crucial for the stimulation of CD4+ T cells. Bryostatin-1, a protein kinase C (PKC) activator, has been considered as a potent chemotherapeutic agent in a variety of in vitro tumor models. Little is known about the role of bryostatin-1 in HLA class II Ag presentation and immune activation in malignant tumors, especially in melanoma. In this study, we show that bryostatin-1 treatment enhances CD4+ T cell recognition of melanoma cells in the context of HLA class II molecules. We also show that bryostatin-1 treatment of melanoma cells increases class II protein levels by upregulating the class II transactivator (CIITA) gene. Flow cytometry and confocal microscopic analyses revealed that bryostatin-1 treatment upregulated the expression of costimulatory molecules (CD80 and CD86) in melanoma cells, which could prolong the interaction of immune cells and tumors. Bryostatin-1 also induced cellular differentiation in melanoma cells, and reduced tumorigenic factors such as pro-cathepsins and matrix-metalloproteinase-9. These data suggest that bryostatin-1 could be used as a chemo-immunotherapeutic agent for reducing tumorigenic potential of melanoma cells while enhancing CD4+ T cell recognition to prevent tumor recurrence. 相似文献