全文获取类型
收费全文 | 300篇 |
免费 | 19篇 |
出版年
2024年 | 1篇 |
2023年 | 3篇 |
2022年 | 5篇 |
2021年 | 7篇 |
2020年 | 3篇 |
2019年 | 8篇 |
2018年 | 10篇 |
2017年 | 5篇 |
2016年 | 13篇 |
2015年 | 8篇 |
2014年 | 20篇 |
2013年 | 22篇 |
2012年 | 30篇 |
2011年 | 30篇 |
2010年 | 15篇 |
2009年 | 19篇 |
2008年 | 17篇 |
2007年 | 14篇 |
2006年 | 10篇 |
2005年 | 9篇 |
2004年 | 9篇 |
2003年 | 6篇 |
2002年 | 6篇 |
2001年 | 1篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1992年 | 4篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 4篇 |
1986年 | 1篇 |
1985年 | 4篇 |
1984年 | 7篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1965年 | 1篇 |
1957年 | 1篇 |
排序方式: 共有319条查询结果,搜索用时 15 毫秒
1.
Amplification and rearrangement in hepatoma cell DNA associated with integrated hepatitis B virus DNA. 总被引:10,自引:1,他引:9
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)
DNA of hepatitis B virus is found to be integrated into the genome of infected human liver cells and may be related to the development of primary liver carcinoma. We have previously reported the cloning of cellular DNA with integrated HBV sequences from the PLC/PRF/5 cell line which derives from a human primary liver carcinoma. Two clones, designated as A-10.7 and A-10.5, and a third uncloned fragment are compared by restriction enzyme mapping, hybridization and nucleotide sequencing. The results indicate that amplification of integrated viral DNA and host flanking regions has occurred, followed by transposition and/or major deletions. The implications of these findings for the development of primary liver carcinoma are discussed. 相似文献
2.
A complete protocol for the expression of recombinant cytochrome c genes from yeast, Drosophila melanogaster, and rat in a yeast strain, GM-3C-2, which does not express its own cytochromes c is described. The construction of the expression vectors, transformation and large-scale growth of the yeast, and preparation and purification of the recombinant cytochromes c are described. It was found that, contrary to the way yeast modifies its own cytochromes c, the recombinant proteins were partially acetylated at their N-terminus, except for the drosophila protein, which remained entirely unblocked. Furthermore, the yeast and rat proteins were close to fully trimethylated at lysine 72, while the drosophila protein could be separated chromatographically into forms containing tri-, di-, mono-, and unmethylated lysine 72 showing corresponding resonances in the NMR spectrum. These observations emphasize that, in employing expression procedures to obtain native or mutant forms of cytochrome c, it is essential to identify the variety and extent of post-translational modifications and to separate the preparation into pure monomolecular species. Otherwise, it may become impossible to distinguish between the influence of a site-directed mutation and unexamined post-translational modifications. 相似文献
3.
P. Suresh Jayasekara Khai Phan Dilip K. Tosh T. Santhosh Kumar Steven M. Moss Guofeng Zhang Joseph J. Barchi Jr. Zhan-Guo Gao Kenneth A. Jacobson 《Purinergic signalling》2013,9(2):183-198
Gold nanoparticles (AuNPs) allow the tuning of pharmacokinetic and pharmacodynamic properties by active or passive targeting of drugs for cancer and other diseases. We have functionalized gold nanoparticles by tethering specific ligands, agonists and antagonists, of adenosine receptors (ARs) to the gold surface as models for cell surface interactions with G protein-coupled receptors (GPCRs). The AuNP conjugates with chain-extended AR ligands alone (PEGylated nucleosides and nonnucleosides, anchored to the Au via thioctic acid) were found to be insoluble in water due to hydrophobic entities in the ligand. Therefore, we added a second, biologically inactive pendant moiety to increase the water solubility, consisting of a PEGylated chain terminating in a carboxylic or phosphate group. The purity and stability of the immobilized biologically active ligand were examined by ultrafiltration and HPLC. Pharmacological receptor binding studies on these GPCR ligand-derivatized AuNPs (2–5 nm in diameter), performed using membranes of mammalian cells stably expressing human A1, A2A, and A3ARs, showed that the desired selectivity was retained with K i values (nanomolar) of A3AR agonist 21b and A2AAR antagonists 24 and 26a of 14 (A3), 34 (A2A), and 69 (A2A), respectively. The corresponding monomers displayed K i values of 37, 61, and 1,420 nM, respectively. In conclusion, we have synthesized stable, water-soluble AuNP derivatives of tethered A3 and A2AAR ligands that retain the biological properties of their monomeric ligands and are intended for therapeutic and imaging applications. This is the first prototypical application to gold carriers of small molecule (nonpeptide) GPCR ligands, which are under investigation for treatment of cancer and inflammatory diseases. 相似文献
4.
Pasupuleti Santhosh Kumar Katari Venkatesh Gopal Sowjenya Lokanathan Srikanth Manne Mudhu Sunitha Uppu Venkateswara Prasad 《Journal of biomolecular structure & dynamics》2013,31(10):2094-2103
Distal renal tubular acidosis (dRTA) is an autosomal recessive syndrome results defect in either proximal tubule bicarbonate reabsorption or in distal tubule H+ secretion and is characterized by severe hyperchloraemic metabolic acidosis in childhood. dRTA is associated with functional variations in the ATP6V1B1 gene encoding β1 subunit of H+-ATPase, key membrane transporters for net acid excretion of α-intercalated cells of medullary collecting ducts. In the present study, a 13-year-old male patient suffering with nephropathy and sensorineural deafness was reported in the Department of Nephrology. We predicted improper functioning of ATP6V1B1 gene could be the reason for diseased condition. Therefore, exons 3, 4, and 7 contributing active site of ATP6V1B1 gene was amplified and sequenced (Accession numbers: KF571726, KM222653). The obtained sequences were BLAST searched against the wild type ATP6V1B1 gene which showed novel mutations c.307 A > G, c.308 C > A, c.310 C > G, c.704 T > C, c.705 G > T, c.709 A > G, c.710 A > G, c.714 G > A, c.716 C > A, c.717delC, c.722 C > G, c.728insG, c.741insT, c.753G > C. These mutations resulted in the expression of truncated protein terminating at Lys 209. The mutated ATP6V1B1structure superimposed with wild type showed extensive variations with RMSD 1.336 Å and could not bind to substrate ADP leading to non-functional ATPase. These results conclusively explain these mutations in ATP6V1B1 gene resulted in structural changes causing accumulation of H+ ions contributing to dRTA with sensorineural deafness. 相似文献
5.
Mayur Parihar Beena Koshy Vivi Miriam Srivastava 《Indian journal of human genetics》2013,19(3):346-348
Chromosomal abnormalities are seen in nearly 1% of live born infants. We report a 5-year-old boy with the clinical features of Down syndrome, which is the most common human aneuploidy. Cytogenetic analysis showed a mosaicism for a double aneuploidy, Down syndrome and XYY. The karyotype was 47, XY,+21[19]/48, XYY,+21[6]. ish XYY (DXZ1 × 1, DYZ1 × 2). Mosaic double aneuploidies are very rare and features of only one of the aneuploidies may predominate in childhood. Cytogenetic analysis is recommended even if the typical features of a recognized aneuploidy are present so that any associated abnormality may be detected. This will enable early intervention to provide the adequate supportive care and management. 相似文献
6.
7.
8.
Basu U Gyrd-Hansen M Baby SM Lozynska O Krag TO Jensen CJ Frödin M Khurana TS 《FEBS letters》2007,581(22):4153-4158
Utrophin is the autosomal homolog of dystrophin, the product of the Duchenne's muscular dystrophy (DMD) locus. Utrophin is of therapeutic interest since its over-expression can compensate dystrophin's absence. Utrophin is enriched at neuromuscular junctions due to heregulin-mediated utrophin-A promoter activation. We demonstrate that heregulin activated MSK1/2 and phosphorylated histone H3 at serine 10 in cultured C2C12 muscle cells, in an ERK-dependent manner. MSK1/2 inhibition suppressed heregulin-mediated utrophin-A activation. MSK1 over-expression potentiated heregulin-mediated utrophin-A activation and chromatin remodeling at the utrophin-A promoter. These results identify MSK1/2 as key effectors modulating utrophin-A expression as well as identify novel targets for DMD therapy. 相似文献
9.
Guduru Moulika Sannapureddy Sailaja Jillela Santhosh Vijitha Putluru Bayapu Reddy Kondala Shanthi Latha Gasthi Venkata Chalapathi Busireddy Sudhakar Reddy 《Luminescence》2022,37(7):1073-1077
Calcium boro fluoro zinc phosphate glasses modified using alkali oxide and doped with Nd3+ and Er3+ ions with the chemical composition of 69.5 (B2O3) + 10 (P2O5) + 10 (CaF2) + 5 (ZnO) + 5 (Na2O/Li2O/K2O) + 0.5 (Er2O3/Nd2O3) were prepared using a conventional melt quenching technique. The results of X-ray diffraction patterns indicated the amorphous nature of all the prepared glasses. The visible–near-infrared red (NIR) absorption spectra of these glasses were analyzed systematically. The NIR emission spectra of Er3+ and Nd3+:calcium boro fluoro zinc phosphate glasses showed prominent emission bands at 1536 nm (4I13/2→4I15/2) and 1069 nm (4F3/2→4I11/2) respectively with λexci = 514.5 nm (Ar+ laser) as the excitation source. 相似文献
10.