全文获取类型
收费全文 | 2450篇 |
免费 | 187篇 |
国内免费 | 1篇 |
出版年
2023年 | 8篇 |
2022年 | 23篇 |
2021年 | 44篇 |
2020年 | 25篇 |
2019年 | 46篇 |
2018年 | 62篇 |
2017年 | 47篇 |
2016年 | 73篇 |
2015年 | 114篇 |
2014年 | 136篇 |
2013年 | 152篇 |
2012年 | 219篇 |
2011年 | 228篇 |
2010年 | 119篇 |
2009年 | 100篇 |
2008年 | 161篇 |
2007年 | 151篇 |
2006年 | 164篇 |
2005年 | 130篇 |
2004年 | 116篇 |
2003年 | 99篇 |
2002年 | 93篇 |
2001年 | 27篇 |
2000年 | 28篇 |
1999年 | 40篇 |
1998年 | 42篇 |
1997年 | 21篇 |
1996年 | 21篇 |
1995年 | 28篇 |
1994年 | 8篇 |
1993年 | 13篇 |
1992年 | 19篇 |
1991年 | 8篇 |
1990年 | 10篇 |
1989年 | 10篇 |
1988年 | 5篇 |
1987年 | 6篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1978年 | 3篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1973年 | 3篇 |
1971年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有2638条查询结果,搜索用时 375 毫秒
901.
Garbaccio RM Huang S Tasber ES Fraley ME Yan Y Munshi S Ikuta M Kuo L Kreatsoulas C Stirdivant S Drakas B Rickert K Walsh ES Hamilton KA Buser CA Hardwick J Mao X Beck SC Abrams MT Tao W Lobell R Sepp-Lorenzino L Hartman GD 《Bioorganic & medicinal chemistry letters》2007,17(22):6280-6285
From HTS lead 1, a novel benzoisoquinolinone class of ATP-competitive Chk1 inhibitors was devised and synthesized via a photochemical route. Using X-ray crystallography as a guide, potency was rapidly enhanced through the installation of a tethered basic amine designed to interact with an acidic residue (Glu91) in the enzyme pocket. Further SAR was explored at the solvent front and near to the H1 pocket and resulted in the discovery of low MW, sub-nanomolar inhibitors of Chk1. 相似文献
902.
Liang R Abrardo L Brady EJ Candelore MR Ding V Saperstein R Tota LM Wright M Mock S Tamvakopolous C Tong S Zheng S Zhang BB Tata JR Parmee ER 《Bioorganic & medicinal chemistry letters》2007,17(3):587-592
A series of conformationally constrained tri-substituted ureas were synthesized, and their potential as glucagon receptor antagonists was evaluated. This effort resulted in the identification of compound 4a, which had a binding IC50 of 4.0 nM and was shown to reduce blood glucose levels at 3 mg/kg in glucagon-challenged mice containing a humanized glucagon receptor. Compound 4a was efficacious in correcting hyperglycemia induced by a high fat diet in transgenic mice at an oral dose as low as 3 mg/kg. 相似文献
903.
Field-selected tolerance to heavy metals has been reported for Orchesella cincta (Arthropoda: Collembola, springtails) populations occurring at metal-contaminated mining sites. Metal tolerance in O. cincta is correlated with heritable increase of excretion efficiency, decrease in cadmium-induced growth reduction, and over-expression of the single copy metallothionein (mt) gene. Although mt plays a major role in cadmium (Cd) detoxification an additional number of gene products may be altered in the tolerant phenotype that influence quantitative traits like excretion efficiency and growth. Using suppression subtractive hybridization analysis (SSH) genes were cloned that showed up- or down-regulation in response to Cd. This study reports about 192 SSH derived cDNA clones, of which 49 were confirmed to be differentially expressed after spot blot analysis. After sequence analysis 19 of the 49 differential clones could be annotated. Real-time RT-PCR of a reference culture and tolerant populations revealed significant gene responses upon Cd exposure. The reference culture showed stress induced gene expression, whereas the tolerant animals maintained normal gene expression or down regulation of cDNAs upon Cd exposure. Seven cDNAs with homology to genes involved in cell signaling, transport and programmed cell death showed an interaction between treatment and population. 相似文献
904.
Screening of a novel octamer peptide, CNSCWSKD, that induces caspase-dependent cell death 总被引:1,自引:0,他引:1
Kaga C Okochi M Nakanishi M Hayashi H Kato R Honda H 《Biochemical and biophysical research communications》2007,362(4):1063-1068
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis to various tumor cells but not in normal cells. We have screened cell death-inducing peptides from the extracellular domain sequence of TRAIL, using a peptide array. Peptides of higher activity were found through amino acid substitution, and the CNSCWSKD peptide induced >90% cell death in treated Jurkat cells. Features of apoptosis, such as DNA fragmentation, activation of caspase, phosphatidylserine externalization, chromatin condensation, and competition with TRAIL for binding to the death receptor (DR) 4 or DR5 were observed, suggesting that this peptide is a TRAIL mimic. Caspase-3 activation was observed in various tumor cells treated with this peptide as well as with TRAIL, while no activation was observed in human normal fibroblasts. The CNSCWSKD peptide is a potential candidate for use in cancer therapy. 相似文献
905.
The 67kDa laminin receptor as a primary determinant of anti-allergic effects of O-methylated EGCG 总被引:1,自引:0,他引:1
Fujimura Y Umeda D Yano S Maeda-Yamamoto M Yamada K Tachibana H 《Biochemical and biophysical research communications》2007,364(1):79-85
Previously we have reported that the O-methylated derivative of (−)-epigallocatechin-3-O-gallate (EGCG), (−)-epigallocatechin-3-O-(3-O-methyl) gallate (EGCG3”Me), possesses anti-allergic activities such as inhibition of histamine release and suppression of the high-affinity IgE receptor (FcεRI) expression. However, the underlying mechanism is still unclear. Recently we have identified the 67 kDa laminin receptor (67LR) as a cell-surface receptor that can mediate biological activities of EGCG. Here we show that the suppression of myosin II regulatory light chain (MRLC) phosphorylation through the cell-surface binding to the 67 LR contributes to the inhibitory effect of EGCG3”Me on the histamine release from the human basophilic KU812 cells. The 67LR also mediated the EGCG3”Me-induced suppression of FcεRI expression by reducing ERK1/2 phosphorylation. These results suggest that anti-allergic effects of EGCG3”Me may be triggered by the inhibition of MRLC or ERK1/2 phosphorylation mediated through the cell-surface 67LR. 相似文献
906.
907.
908.
Burden of Chagas disease in Brazil, 1990–2016: findings from the Global Burden of Disease Study 2016
Francisco Rogerlândio Martins-Melo Mariângela Carneiro Antonio Luiz Pinho Ribeiro Juliana Maria Trindade Bezerra Guilherme Loureiro Werneck 《International journal for parasitology》2019,49(3-4):301-310
Chagas disease continues to be an important cause of morbidity, mortality and disability in several Latin American countries, including Brazil. Using findings from the Global Burden of Disease Study 2016 (GBD, 2016), we present years of life lost, years lived with disability, and disability-adjusted life years due to Chagas disease in Brazil, by sex, age group, and Brazilian states, from 1990 to 2016. Results are reported in absolute numbers and age-standardized rates (per 100,000 population) with 95% uncertainty intervals. In 2016, 141,640 disability-adjusted life years (95% uncertainty intervals: 129,065–155,941) due to Chagas disease were estimated in Brazil, with a relative reduction of 36.7% compared with 1990 (223,879 disability-adjusted life years (95% uncertainty intervals: 209,372–238,591)). Age-standardized disability-adjusted life year rates declined at the national level (?69.7%) and in all Brazilian states between 1990 and 2016, but with different regional patterns. The decrease in the disability-adjusted life year rates was driven primarily by a consistent reduction in the years of life lost rates, the main component of total disability-adjusted life years for Chagas disease. The highest fatal and non-fatal burden due to Chagas disease was observed among males, the elderly, and in those Brazilian states encompassing important endemic areas for vector transmission in the past. Despite the consistent reduction in its burden during the period, Chagas disease is still an important and neglected cause of health lost due to premature mortality and disability in Brazil. Efforts should be made to maintain the political interest and sustainability of surveillance and control actions for Chagas disease, prevent the risk of re-emergence of vector transmission in endemic areas, and provide health care to chronically infected individuals, including early diagnosis and treatment interventions. 相似文献
909.
Genetic and morphological variability of the European mudminnow Umbra krameri (Teleostei,Umbridae) in Serbia and in Bosnia and Herzegovina,a basis for future conservation activities
下载免费PDF全文
![点击此处可从《Journal of fish biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
S. Marić A. Snoj N. Sekulić J. Krpo‐Ćetković R. Šanda V. Jojić 《Journal of fish biology》2015,86(5):1534-1548
As a basis for future conservation activities, the genetic and external body morphology variability of the European mudminnow Umbra krameri, a highly endangered fish species in Serbia and in Bosnia and Herzegovina, was determined for existing populations with the use of molecular markers (mitochondrial and microsatellite DNA) and geometric morphometric methods. Mitochondrial DNA cytochrome b gene analysis revealed two previously undescribed haplotypes: Da1 (the Lugomir population from the Danube River basin) and Sa1 (the Bakreni Batar and the Gromi?elj populations from the Sava River system), with a corresponding genetic distance of 0·7%. Paired values of FST and DAS distances for microsatellite marker data show that the difference between the Danube and the Sava populations is seven to nine times higher than the difference between the populations within the Sava River system. Geometric morphometric analyses also support a clear separation of the Lugomir population from the Bakreni Batar and the Gromi?elj populations. The analysis of the body shape variation, however, indicates a significant difference between the two genetically indistinguishable Sava populations. The observed genetic and phenetic relationships of the analysed mudminnow populations most probably represent a consequence of historical, geographical and ecological factors. These results will offer guidelines for future protection, conservation and sustainable management of this species in the region. 相似文献
910.