全文获取类型
收费全文 | 5097篇 |
免费 | 439篇 |
国内免费 | 297篇 |
出版年
2024年 | 9篇 |
2023年 | 133篇 |
2022年 | 138篇 |
2021年 | 212篇 |
2020年 | 236篇 |
2019年 | 297篇 |
2018年 | 271篇 |
2017年 | 202篇 |
2016年 | 246篇 |
2015年 | 255篇 |
2014年 | 369篇 |
2013年 | 522篇 |
2012年 | 208篇 |
2011年 | 224篇 |
2010年 | 164篇 |
2009年 | 197篇 |
2008年 | 196篇 |
2007年 | 210篇 |
2006年 | 193篇 |
2005年 | 147篇 |
2004年 | 152篇 |
2003年 | 132篇 |
2002年 | 132篇 |
2001年 | 87篇 |
2000年 | 63篇 |
1999年 | 59篇 |
1998年 | 74篇 |
1997年 | 46篇 |
1996年 | 29篇 |
1995年 | 54篇 |
1994年 | 53篇 |
1993年 | 45篇 |
1992年 | 33篇 |
1991年 | 34篇 |
1990年 | 34篇 |
1989年 | 33篇 |
1988年 | 38篇 |
1987年 | 34篇 |
1986年 | 23篇 |
1985年 | 45篇 |
1984年 | 58篇 |
1983年 | 40篇 |
1982年 | 29篇 |
1981年 | 26篇 |
1980年 | 19篇 |
1979年 | 9篇 |
1978年 | 9篇 |
1977年 | 7篇 |
1976年 | 4篇 |
1973年 | 2篇 |
排序方式: 共有5833条查询结果,搜索用时 187 毫秒
61.
62.
63.
《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):843-847
Expression of MDR1 and MRP genes in patients with low‐grade and high‐grade non‐Hodgkin's lymphomas with primary bone marrow involvement before and after chemotherapy was investigated. The data demonstrate that overexpression of MDR1 and MRP genes in hematological malignancies elevates in patients after chemotherapy and correlates with poor clinic prognosis and more frequent recurrences of the malignancies. 相似文献
64.
《Cell cycle (Georgetown, Tex.)》2013,12(8):1479-1480
Comment on: Vicente-Dueñas C, et al. Oncotarget 2012; Epub ahead of print; PMID:22408137. 相似文献
65.
《Bioscience, biotechnology, and biochemistry》2013,77(3):772-782
The yeast MAPKKK Ste11 activates three MAP kinase pathways, including pheromone signaling, osmosensing, and pseudohyphal/invasive growth pathways. We identified two chemical compounds, BTB03006 and GK03225, that suppress growth defects induced by Ste11 activation in diploid yeast cells. BTB03006, but not GK03225, was found to suppress growth defects induced by both α-factor and Ste4 Gβ overexpression in the pheromone signaling pathway, suggesting that GK03225 is an osmosensing pathway-specific inhibitor. We also performed genome-wide suppressor analysis for Ste11 activation, using a yeast deletion strains collection, and identified PBS2 and HOG1, and several genes associated with chaperone functions, which represent potential target proteins of the drugs screened from Ste11 activation. GK03225 possesses an Iressa-like quinazoline ring structure, and its chemical analog, 11N-078, suppresses c-Abl human tyrosine kinase activity. These results suggest that drug screening in yeast can identify human tyrosine kinase inhibitors and other drugs for human diseases. 相似文献
66.
67.
《Expert review of proteomics》2013,10(5):561-572
Cystine-knot miniproteins, also known as knottins, constitute a large family of structurally related peptides with diverse amino acid sequences and biological functions. Knottins have emerged as attractive candidates for drug development as they potentially fill a niche between small molecules and protein biologics, offering drug-like properties and the ability to bind to clinical targets with high affinity and selectivity. Due to their extremely high stability and unique structural features, knottins also demonstrate promise in addressing challenging drug development goals, including the potential for oral delivery and the ability to access intracellular drug targets. Several naturally-occurring knottins have recently received approval for treating chronic pain and irritable bowel syndrome, while others are under development for tumor imaging applications. To expand beyond nature’s repertoire, rational and combinatorial protein engineering methods are generating tumor-targeting knottins for use as cancer diagnostics and therapeutics. 相似文献
68.
Aurora B kinase is an integral regulator of cytokinesis, as it stabilizes the intercellular canal within the midbody to ensure proper chromosomal segregation during cell division. Here we identified that the ubiquitin E3 ligase complex SCFFBXL2 mediates Aurora B ubiquitination and degradation within the midbody, which is sufficient to induce mitotic arrest and apoptosis. Three molecular acceptor sites (K102, K103 and K207) within Aurora B protein were identified as important sites for its ubiquitination. A triple Lys mutant of Aurora B (K102/103/207R) exhibited optimal resistance to SCFFBXL2-directed polyubiquitination, and overexpression of this variant resulted in a significant delay in anaphase onset, resulting in apoptosis. A unique small molecule F-box/LRR-repeat protein 2 (FBXL2) activator, BC-1258, stabilized and increased levels of FBXL2 protein that promoted Aurora B degradation, resulting in tetraploidy, mitotic arrest and apoptosis of tumorigenic cells, and profoundly inhibiting tumor formation in athymic nude mice. These findings uncover a new proteolytic mechanism targeting a key regulator of cell replication that may serve as a basis for chemotherapeutic intervention in neoplasia. 相似文献
69.
《Bioorganic & medicinal chemistry letters》2014,24(7):1820-1824
The design and synthesis of a series of novel tricyclic IAP inhibitors is reported. Rapid assembly of the core tricycle involved two key steps: Rh-catalyzed hydrogenation of an unsaturated bicyclic ring system and a Ru-catalyzed ring closing alkene metathesis reaction. The final Smac mimetics bind to cIAP1 and XIAP BIR3 domains and elicit the desired phenotype in cellular proliferation assays. Dimeric IAP inhibitors were found to possess nanomolar potency in a cellular proliferation assay and favourable in vitro drug-like properties. 相似文献
70.
《Bioorganic & medicinal chemistry letters》2014,24(11):2493-2496
Bromodomains (BRDs) recognize acetyl-lysine modified histone tails mediating epigenetic processes. BRD4, a protein containing two bromodomains, has emerged as an attractive therapeutic target for several types of cancer as well as inflammatory diseases. Using a fragment-based in silico screening approach, we identified two small molecules that bind to the first bromodomain of BRD4 with low-micromolar affinity and favorable ligand efficiency (0.37 kcal/mol per non-hydrogen atom), selectively over other families of bromodomains. Notably, the hit rate of the fragment-based in silico approach is about 10% as only 24 putative inhibitors, from an initial library of about 9 million molecules, were tested in vitro. 相似文献