全文获取类型
收费全文 | 60298篇 |
免费 | 4615篇 |
国内免费 | 3210篇 |
出版年
2024年 | 78篇 |
2023年 | 488篇 |
2022年 | 967篇 |
2021年 | 2235篇 |
2020年 | 1570篇 |
2019年 | 1957篇 |
2018年 | 2134篇 |
2017年 | 1579篇 |
2016年 | 2383篇 |
2015年 | 3641篇 |
2014年 | 4159篇 |
2013年 | 4518篇 |
2012年 | 5386篇 |
2011年 | 4889篇 |
2010年 | 3186篇 |
2009年 | 2700篇 |
2008年 | 3477篇 |
2007年 | 3089篇 |
2006年 | 2705篇 |
2005年 | 2458篇 |
2004年 | 2210篇 |
2003年 | 1920篇 |
2002年 | 1691篇 |
2001年 | 1318篇 |
2000年 | 1174篇 |
1999年 | 984篇 |
1998年 | 540篇 |
1997年 | 498篇 |
1996年 | 446篇 |
1995年 | 357篇 |
1994年 | 338篇 |
1993年 | 247篇 |
1992年 | 404篇 |
1991年 | 331篇 |
1990年 | 235篇 |
1989年 | 229篇 |
1988年 | 169篇 |
1987年 | 181篇 |
1986年 | 156篇 |
1985年 | 131篇 |
1984年 | 108篇 |
1983年 | 78篇 |
1982年 | 72篇 |
1981年 | 54篇 |
1979年 | 55篇 |
1978年 | 49篇 |
1976年 | 46篇 |
1975年 | 52篇 |
1973年 | 44篇 |
1972年 | 41篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
51.
Jian‐Yong Guo Yong‐Sheng Wang Tian Chen Xiao‐Xu Jiang Ping Wu Tao Geng Zhong‐Hua Pan Meng‐Ke Shang Cheng‐Xiang Hou Kun Gao Xi‐Jie Guo 《Insect Science》2020,27(3):449-462
Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) is a major pathogen of the economic insect silkworm, Bombyx mori. Virus‐encoded microRNAs (miRNAs) have been proven to play important roles in host–pathogen interactions. In this study we identified a BmCPV‐derived miRNA‐like 21 nt small RNA, BmCPV‐miR‐1, from the small RNA deep sequencing of BmCPV‐infected silkworm larvae by stem‐loop quantitative real‐time PCR (qPCR) and investigated its functions with qPCR and lentiviral expression systems. Bombyx mori inhibitor of apoptosis protein (BmIAP) gene was predicted by both target prediction software miRanda and Targetscan to be one of its target genes with a binding site for BmCPV‐miR‐1 at the 5′ untranslated region. It was found that the expression of BmCPV‐miR‐1 and its target gene BmIAP were both up‐regulated in BmCPV‐infected larvae. At the same time, it was confirmed that BmCPV‐miR‐1 could up‐regulate the expression of BmIAP gene in HEK293T cells with lentiviral expression systems and in BmN cells by transfecting mimics. Furthermore, BmCPV‐miR‐1 mimics could up‐regulate the expression level of BmIAP gene in midgut and fat body in the silkworm. In the midgut of BmCPV‐infected larvae, BmCPV‐miR‐1 mimics could be further up‐regulated and inhibitors could lower the virus‐mediated expression of BmIAP gene. With the viral genomic RNA segments S1 and S10 as indicators, BmCPV‐miR‐1 mimics could up‐regulate and inhibitors down‐regulate their replication in the infected silkworm. These results implied that BmCPV‐miR‐1 could inhibit cell apoptosis in the infected silkworm through up‐regulating BmIAP expression, providing the virus with a better cell circumstance for its replication. 相似文献
52.
53.
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
54.
55.
The study was designed to determine whether methionine-enkephalin (M-ENK) was present in the digestive system of the scallop
Chlamys farreri and investigate the effects of M-ENK on the activity of amylase, protease and lipase in the digestive system of C. farreri. The results indicated that M-ENK-like material was present in the epithelium and connective tissue of labial palps, mouth
labia, stomach, intestine, rectum, and hepatopancreas of the scallop C. farreri. Moreover, it was also found that many isolated small cells showing M-ENK-like immunoreactivity were scattered in the epithelial
layer of intestine, and many isolated big epithelial cells showing M-ENK-like immunoreactivity were scattered in tubules of
hepatopancreas of the scallop. The activity levels of amylase and lipase in crystalline style, hepatopancreas and intestine
were enhanced at 1 h after injection of exogenous M-ENK into adductor muscle of the scallops, whereas protease activity levels
were significantly suppressed. Our report constitutes the first characterization of M-ENK in the digestive system of scallop
C. farreri and investigates the effects of M-ENK on the activities of digestive enzymes of mollusk for the first time. The results suggest
an involvement of M-ENK in the functional regulation of the digestive system of C. farreri. 相似文献
56.
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
57.
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
58.
59.
Wei Liu Yaoting Sun Weigang Ge Fangfei Zhang Lin Gan Yi Zhu Tiannan Guo Kexin Liu 《Molecular & cellular proteomics : MCP》2022,21(2):100187
Drug resistance is a critical obstacle to effective treatment in patients with chronic myeloid leukemia. To understand the underlying resistance mechanisms in response to imatinib mesylate (IMA) and adriamycin (ADR), the parental K562 cells were treated with low doses of IMA or ADR for 2 months to generate derivative cells with mild, intermediate, and severe resistance to the drugs as defined by their increasing resistance index. PulseDIA-based (DIA [data-independent acquisition]) quantitative proteomics was then employed to reveal the proteome changes in these resistant cells. In total, 7082 proteins from 98,232 peptides were identified and quantified from the dataset using four DIA software tools including OpenSWATH, Spectronaut, DIA-NN, and EncyclopeDIA. Sirtuin signaling pathway was found to be significantly enriched in both ADR-resistant and IMA-resistant K562 cells. In particular, isocitrate dehydrogenase (NADP(+)) 2 was identified as a potential drug target correlated with the drug resistance phenotype, and its inhibition by the antagonist AGI-6780 reversed the acquired resistance in K562 cells to either ADR or IMA. Together, our study has implicated isocitrate dehydrogenase (NADP(+)) 2 as a potential target that can be therapeutically leveraged to alleviate the drug resistance in K562 cells when treated with IMA and ADR. 相似文献
60.
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