全文获取类型
收费全文 | 29994篇 |
免费 | 2317篇 |
国内免费 | 27篇 |
出版年
2023年 | 84篇 |
2022年 | 149篇 |
2021年 | 565篇 |
2020年 | 355篇 |
2019年 | 438篇 |
2018年 | 722篇 |
2017年 | 567篇 |
2016年 | 946篇 |
2015年 | 1550篇 |
2014年 | 1683篇 |
2013年 | 1958篇 |
2012年 | 2486篇 |
2011年 | 2320篇 |
2010年 | 1528篇 |
2009年 | 1329篇 |
2008年 | 1908篇 |
2007年 | 1680篇 |
2006年 | 1498篇 |
2005年 | 1380篇 |
2004年 | 1324篇 |
2003年 | 1103篇 |
2002年 | 1088篇 |
2001年 | 823篇 |
2000年 | 799篇 |
1999年 | 560篇 |
1998年 | 250篇 |
1997年 | 200篇 |
1996年 | 170篇 |
1995年 | 165篇 |
1994年 | 124篇 |
1993年 | 123篇 |
1992年 | 248篇 |
1991年 | 201篇 |
1990年 | 167篇 |
1989年 | 187篇 |
1988年 | 148篇 |
1987年 | 143篇 |
1986年 | 134篇 |
1985年 | 125篇 |
1984年 | 103篇 |
1983年 | 80篇 |
1982年 | 63篇 |
1980年 | 45篇 |
1979年 | 71篇 |
1978年 | 72篇 |
1977年 | 53篇 |
1976年 | 73篇 |
1975年 | 64篇 |
1974年 | 54篇 |
1973年 | 60篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
31.
32.
33.
34.
35.
Secretion of Recombinant Pediocin PA-1 by Bifidobacterium longum, Using the Signal Sequence for Bifidobacterial α-Amylase 下载免费PDF全文
Gi-Seong Moon Yu-Ryang Pyun Myeong Soo Park Geun Eog Ji Wang June Kim 《Applied microbiology》2005,71(9):5630-5632
A recombinant DNA, encoding the chimeric protein of the signal sequence for bifidobacterial α-amylase mature pediocin PA-1, was introduced into Bifidobacterium longum MG1. Biologically active pediocin PA-1 was successfully secreted from the strain and showed bactericidal activity against Listeria monocytogenes and the same molecular mass as native pediocin PA-1. 相似文献
36.
The amounts of cAMP and cGMP in the rat pinealocyte are regulated by norepinephrine acting through synergistic dual receptor mechanisms involving alpha 1- and beta-adrenoceptors (Vanecek, J., Sugden, D., Weller, J.L., and Klein, D.C. (1985) Endocrinology 116, 2167-2173; Sugden, L., Sugden, D., and Klein, D.C. (1986) J. Biol. Chem. 261, 11608-11612). Based on the available evidence, it appears that Ca2+-phospholipid-dependent protein kinase is involved in the alpha 1-adrenergic potentiation of beta-adrenergic stimulation of cAMP, but not in the stimulation of cGMP (Sugden, D., Vanecek, J., Klein, D.C., Thomas, T.P., and Anderson, W.B. (1985) Nature 314, 359-361). In the present study the role of protein kinase C in the adrenergic stimulation of cGMP was reinvestigated, with the purpose of determining whether protein kinase C activators would potentiate the effects of beta-adrenergic agonists on cGMP if cells were also treated with agents known to elevate intracellular free Ca2+. The protein kinase C activator 4 beta-phorbol 12-myristate 13-acetate (PMA) markedly elevated the cGMP content of beta-adrenergically stimulated pinealocytes which had also been treated with 1 microM A23187, 15 mM K+, or 1 microM ouabain. The effects of A23187 were blocked by EGTA and those of K+ were blocked by nifedipine, establishing the involvement of Ca2+. The stimulatory effects of PMA on cGMP accumulation were mimicked by other protein kinase C activators. PMA also stimulated cGMP accumulation in cells treated with cholera toxin (1 microgram/ml) and A23187 (1 microM), but not in cells treated only with cholera toxin. These results suggest that protein kinase C, which is activated in the pinealocyte by the alpha-adrenergic agonist phenylephrine, is probably involved in the adrenergic regulation of cGMP accumulation at a step distal to receptor activation. 相似文献
37.
Jin-Young Park 《Analytical biochemistry》2009,394(2):217-6489
Transglutaminases (TGs), a family of calcium-dependent transamidating enzymes, are involved in functions such as apoptosis and inflammation and play a role in autoimmune diseases and neurodegenerative disorders. In this study, we describe a novel array-based approach to rapidly determine in situ TG activity in human umbilical vein endothelial cells and J82 human bladder carcinoma cells. Amine arrays were fabricated by immobilizing 3-aminopropyltrimethoxysilane on glass slides. The assay was specific and highly reproducible. The average coefficient of variation betweens spots was 2.6% (n = 3 arrays), and the average correlation coefficients between arrays and between arrays/reactions were 0.998 and 0.976, respectively (n = 3 arrays). The assay was successfully applied to detect changes in TG activity induced by maitotoxin and to analyze inhibition of the TG activation with cystamine and monodansyl cadaverine. In addition, the assay demonstrated that intracellular reactive oxygen species regulate the maitotoxin-induced activation of TG. Thus, the array-based in situ TG activity assay constitutes a rapid and high-throughput approach to investigating the roles of TGs in cell signaling. 相似文献
38.
Kathryn S. Evans Janneke Wit Lewis Stevens Steffen R. Hahnel Briana Rodriguez Grace Park Mostafa Zamanian Shannon C. Brady Ellen Chao Katherine Introcaso Robyn E. Tanny Erik C. Andersen 《PLoS pathogens》2021,17(3)
Parasitic nematodes cause a massive worldwide burden on human health along with a loss of livestock and agriculture productivity. Anthelmintics have been widely successful in treating parasitic nematodes. However, resistance is increasing, and little is known about the molecular and genetic causes of resistance for most of these drugs. The free-living roundworm Caenorhabditis elegans provides a tractable model to identify genes that underlie resistance. Unlike parasitic nematodes, C. elegans is easy to maintain in the laboratory, has a complete and well annotated genome, and has many genetic tools. Using a combination of wild isolates and a panel of recombinant inbred lines constructed from crosses of two genetically and phenotypically divergent strains, we identified three genomic regions on chromosome V that underlie natural differences in response to the macrocyclic lactone (ML) abamectin. One locus was identified previously and encodes an alpha subunit of a glutamate-gated chloride channel (glc-1). Here, we validate and narrow two novel loci using near-isogenic lines. Additionally, we generate a list of prioritized candidate genes identified in C. elegans and in the parasite Haemonchus contortus by comparison of ML resistance loci. These genes could represent previously unidentified resistance genes shared across nematode species and should be evaluated in the future. Our work highlights the advantages of using C. elegans as a model to better understand ML resistance in parasitic nematodes. 相似文献
39.
40.
J-H Kim K W Park E-W Lee W-S Jang J Seo S Shin K-A Hwang J Song 《Cell death and differentiation》2014,21(4):594-603
The central regulator of adipogenesis, PPARγ, is a nuclear receptor that is linked to obesity and metabolic diseases. Here we report that MKRN1 is an E3 ligase of PPARγ that induces its ubiquitination, followed by proteasome-dependent degradation. Furthermore, we identified two lysine sites at 184 and 185 that appear to be targeted for ubiquitination by MKRN1. Stable overexpression of MKRN1 reduced PPARγ protein levels and suppressed adipocyte differentiation in 3T3-L1 and C3H10T1/2 cells. In contrast, MKRN1 depletion stimulated adipocyte differentiation in these cells. Finally, MKRN1 knockout MEFs showed an increased capacity for adipocyte differentiation compared with wild-type MEFs, with a concomitant increase of PPARγ and adipogenic markers. Together, these data indicate that MKRN1 is an elusive PPARγ E3 ligase that targets PPARγ for proteasomal degradation by ubiquitin-dependent pathways, and further depict MKRN1 as a novel target for diseases involving PPARγ. 相似文献