全文获取类型
收费全文 | 19479篇 |
免费 | 1491篇 |
国内免费 | 1755篇 |
出版年
2024年 | 67篇 |
2023年 | 290篇 |
2022年 | 509篇 |
2021年 | 683篇 |
2020年 | 580篇 |
2019年 | 874篇 |
2018年 | 812篇 |
2017年 | 489篇 |
2016年 | 546篇 |
2015年 | 712篇 |
2014年 | 1304篇 |
2013年 | 1394篇 |
2012年 | 932篇 |
2011年 | 1273篇 |
2010年 | 936篇 |
2009年 | 1006篇 |
2008年 | 1001篇 |
2007年 | 1125篇 |
2006年 | 979篇 |
2005年 | 859篇 |
2004年 | 720篇 |
2003年 | 609篇 |
2002年 | 587篇 |
2001年 | 378篇 |
2000年 | 365篇 |
1999年 | 332篇 |
1998年 | 379篇 |
1997年 | 272篇 |
1996年 | 280篇 |
1995年 | 292篇 |
1994年 | 223篇 |
1993年 | 201篇 |
1992年 | 194篇 |
1991年 | 175篇 |
1990年 | 147篇 |
1989年 | 119篇 |
1988年 | 119篇 |
1987年 | 96篇 |
1986年 | 65篇 |
1985年 | 110篇 |
1984年 | 156篇 |
1983年 | 123篇 |
1982年 | 137篇 |
1981年 | 59篇 |
1980年 | 54篇 |
1979年 | 51篇 |
1978年 | 41篇 |
1977年 | 19篇 |
1976年 | 14篇 |
1974年 | 11篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
11.
12.
13.
14.
15.
A bacterial clone carrying sequences coding for elongation factor EF-1 alpha from Artemia 总被引:2,自引:0,他引:2
A bacterial cDNA clone was identified carrying one third of the nucleotides coding for elongation factor EF-1 alpha from the brine shrimp Artemia. The sequence of codons corresponds with the known sequence of amino acids of EF-1 alpha in the region involved. 相似文献
16.
J.N. Beresford J.A. Gallagher M. Gowen M. Couch J. Poser D.D. Wood R.G.G. Russell 《Biochimica et Biophysica Acta (BBA)/General Subjects》1984,801(1):58-65
Cultural adherent human mononuclear cells produce factor(s) which stimulate the release of calcium from new-born mouse calvaria in organ culture. This stimulation of bone resorption is accompanied by an inhibition of the incorporation of [3H]proline into collagen which is independent of increased prostaglandin production by the bone. When human osteoblast-like cells are treated with conditioned medium from human mononuclear cells, collagen accounts for a decreased proportion of the protein synthesised. This effect on matrix synthesis is not accompanied by an inhibitory action of the monocyte-conditioned medium preparations on net cell proliferation. In human osteoblast-like cell cultures, partially purified human interleukin 1 also inhibits the production of the bone-specific protein osteocalcin in a dose-dependent fashion. These observations are consistent with the hypothesis that products of human monocytes similar to, or identical with, human interleukin 1 may be important regulators of bone metabolism and may contribute to the bone loss seen in diseases such as chronic rheumatoid arthritis. 相似文献
17.
18.
Expression of alternatively spliced mRNA variants at specific stages of development or in specific cells and tissues contributes to the functional diversity of the human genome. Aberrations in alternative splicing were found as a cause or a contributing factor to the development, progression, or maintenance of numerous diseases. The use of antisense oligonucleotides (ON) to modify aberrant expression patterns of alternatively spliced mRNAs is a novel means of potentially controlling such diseases. Oligonucleotides can be designed to repair genetic mutations, to modify genomic sequences in order to compensate for gene deletions, or to modify RNA processing in order to improve the effects of the underlying gene mutation. Steric block ON approach have proven to be effective in experimental model for various diseases. Here, we describe our experience in investigating two strategies for ON delivery: ON conjugation with basic peptides and lipid-based particulate system (lipoplex). Basic peptides or Cell Penetrating Peptides (CPP) such as the TAT-derived peptide appear to circumvent many problems associated with ON and drug delivery. This strategy may represent the next paradigm in our ability to modulate cell function and offers a unique avenue for the treatment of disease. Lipoplexes result from the intimate interaction of ON with cationic lipids leading to ON carrying particles able to be taken up by cells and to release ON in the cytoplasm. We have used as an experimental model the correction of a splicing alteration of the mutated β-globin intron causing thalassemia. Data on cell penetration and efficacy of correction of specific steric block ON delivered either by basic peptides or lipoplex are described. A comparison of the properties of both delivery systems is made respective to the use of this new class of therapeutic molecules. 相似文献
19.
Harry Le Vine Pedro Cuatrecasas 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,672(3):248-261
A cytosolic, macromolecular factor required for the cholera toxin-dependent activation of pigeon erythrocyte adenylate cyclase and cholera toxin-dependent ADP-ribosylation of a membrane-bound 43 000 dalton polypeptide has been purified 1100-fold from horse erythrocyte cytosol using organic solvent precipitation and heat treatment. This factor, 13 000 daltons, does not absorb to anionic or cationic exchange resins, is sensitive to trypsin or 10% trichloroacetic acid and is not extractable by diethyl ether. Activation of adenylate cyclase by cholera toxin requires the simultaneous presence of ATP (including possible trace GTP), NAD+, dithiothreitol, cholera toxin, membranes and the cytosolic macromolecular factor. Reversal of cholera toxin activation of adenylate cyclase, and of the toxin-dependent ADP-ribosylation, requires the presence of the cytosolic factor. The ability of the purified cytosolic factor to influence the hormonal sensitivity of liver membrane adenylate cyclase may provide clues to its physiological functions. 相似文献
20.
Binding of B‐cell maturation antigen to B‐cell activating factor induces survival of multiple myeloma cells by activating Akt and JNK signaling pathways 下载免费PDF全文
Xianjuan Shen Yuehua Guo Jing Qi Wei Shi Xinhua Wu Shaoqing Ju 《Cell biochemistry and function》2016,34(2):104-110
B‐cell maturation antigen (BCMA) is expressed on normal and malignant plasma cells and represents a potential target for therapeutic intervention. In this study, we characterized the mechanism underlying the protein kinase B (Akt) and c‐Jun N‐terminal kinase (JNK) pathways and BCMA interactions in regulating multiple myeloma (MM) cell survival. It was found that the expression levels of B cell‐activating factor (BAFF) and BCMA were increased in MM cells as compared with those in normal controls. The proliferation of U266 cells was induced by recombinant human BAFF (rhBAFF) and could also be decreased by BCMA siRNA. The expression of Bcl‐2 protein was up‐regulated, and Bax protein was down‐regulated after rhBAFF treatment, which could be reversed by BCMA siRNA. Similarly, the protein p‐JNK and p‐Akt were activated by rhBAFF and could be changed by BCMA siRNA. In addition, the BCMA mRNA and protein expression levels were decreased after treatment with Akt and JNK pathway inhibitors. These results suggest that Akt and JNK pathways are involved in the regulation of BCMA. A novel BAFF/BCMA signalling pathway in MM may be a new therapeutic target for MM. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献