全文获取类型
收费全文 | 3861篇 |
免费 | 425篇 |
国内免费 | 613篇 |
专业分类
4899篇 |
出版年
2024年 | 40篇 |
2023年 | 104篇 |
2022年 | 222篇 |
2021年 | 286篇 |
2020年 | 209篇 |
2019年 | 222篇 |
2018年 | 242篇 |
2017年 | 153篇 |
2016年 | 184篇 |
2015年 | 283篇 |
2014年 | 367篇 |
2013年 | 338篇 |
2012年 | 387篇 |
2011年 | 340篇 |
2010年 | 232篇 |
2009年 | 210篇 |
2008年 | 216篇 |
2007年 | 174篇 |
2006年 | 150篇 |
2005年 | 104篇 |
2004年 | 88篇 |
2003年 | 96篇 |
2002年 | 61篇 |
2001年 | 13篇 |
2000年 | 12篇 |
1999年 | 24篇 |
1998年 | 14篇 |
1997年 | 17篇 |
1996年 | 16篇 |
1995年 | 10篇 |
1994年 | 12篇 |
1993年 | 9篇 |
1992年 | 13篇 |
1991年 | 7篇 |
1990年 | 11篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 6篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1972年 | 2篇 |
1970年 | 3篇 |
1967年 | 1篇 |
排序方式: 共有4899条查询结果,搜索用时 11 毫秒
911.
912.
Wu Zhang Yanyan Ji Nan Shen Qingzhu Jia Wang Chang 《Saudi Journal of Biological Sciences》2021,28(1):163-169
The photodegradation of 2-chlorobenzoic acid (2-CBA) in suspensions of TiO2 was examined under different operational parameters. The optimal condition could be obtained through the experiment, i.e. that the concentration of 2-CBA was 30 mg/L and the dosing quantity of TiO2 was 0.01 g under UV light in the case of pH 3.5. Above reaction process was in accordance with first order kinetics model. The influence on photocatalytic degradation caused by typical anions in eutrophicated water body such as NO3− and H2PO4− was explored in this work, which revealed that both two anions had inhibitory effect on the degradation process. In addition, alcohol was introduced into the process to identify the degradation mechanism of 2-CBA with TiO2, and the reaction route of 2-CBA could be predicted through the analysis on the intermediate. 相似文献
913.
Nan Song Lihong Chen Xingmei Ren Nicholas R. Waterfield Jian Yang Guowei Yang 《PLoS pathogens》2021,17(2)
Tc toxin is an exotoxin composed of three subunits named TcA, TcB and TcC. Structural analysis revealed that TcA can form homopentamer that mediates the cellular recognition and delivery processes, thus contributing to the host tropism of Tc toxin. N-glycans and heparan sulfates have been shown to act as receptors for several Tc toxins. Here, we performed two independent genome-wide CRISPR-Cas9 screens, and have validated glycans and sulfated glycosaminoglycans (sGAGs) as Tc toxin receptors also for previously uncharacterized Tc toxins. We found that TcdA1 form Photorhabdus luminescens W14 (TcdA1W14) can recognize N-glycans via the RBD-D domain, corroborating previous findings. Knockout of N-glycan processing enzymes specifically blocks the intoxication of TcdA1W14-assembled Tc toxin. On the other hand, our results showed that sGAG biosynthesis pathway is involved in the cell surface binding of TcdA2TT01 (TcdA2 from P. luminescens TT01). Competition assays and biolayer interferometry demonstrated that the sulfation group in sGAGs is required for the binding of TcdA2TT01. Finally, based on the conserved domains of representative TcA proteins, we have identified 1,189 putative TcAs from 1,039 bacterial genomes. These TcAs are categorized into five subfamilies. Each subfamily shows a good correlation with both genetic organization of the TcA protein(s) and taxonomic origin of the genomes, suggesting these subfamilies may utilize different mechanisms for cellular recognition. Taken together, our results support the previously described two different binding modalities of Tc toxins, leading to unique host targeting properties. We also present the bioinformatics data and receptor screening strategies for TcA proteins, provide new insights into understanding host specificity and biomedical applications of Tc toxins. 相似文献
914.
Nan Cheng Chang Jin Ping Jin Dan Zhu Zuoxu Hou 《Journal of cellular and molecular medicine》2021,25(13):6137-6147
High glucose promoted expression of AKT3, a direct target gene of miR-29b, by regulating circHIPK3 that functioned as ceRNA to sponge and down-regulate miR-29b. As a potential target gene of miR-29b, AKT3 plays a crucial role in the pathogenesis of myocardial ischaemia/reperfusion (I/R) injury, and this study aimed to investigate the potential role of high glucose in the outcome of I/R injury. qPCR and luciferase assay were carried out to investigate the relationship between the expression of circHIPK3, miR-29b and ATK3 mRNA. Immunohistochemistry and TUNEL were performed to analyse the relationship between AKT3 expression and apoptosis of myocardiocytes in vivo. No obvious difference in myocardial functions was observed between I/R and control rats under hyperglycaemia (HG) and normal glucose (NG) conditions, except that the infarct size/area at risk (IS/AR) ratio and the amount of h-FABP expression were different under HG and NG conditions. The expression of circHIPK3 and ATK3 was significantly elevated in the rats preconditioned by NG, whereas the expression of miR-29a was remarkably decreased. Meanwhile, the apoptosis of myocardial tissue was reduced in the rats preconditioned by NG. Luciferase assay confirmed that miR-29a played a repressive role in the expression of circHIPK3 and ATK3. And subsequent study indicated that the over-expressed AKT3 could rescue the increased cell apoptosis rate induced by the knockdown of circHIPK3. In this study, we demonstrated that high glucose protects cardiomyocytes against I/R associated injury by suppressing apoptosis and high glucose promoted the expression of AKT3 by regulating the expression of circHIPK3/miR-29b. 相似文献
915.
916.
917.
Nan Wu Xiao-Fan Xu Jia-Qi Xin Jian-Wei Fan Yuan-Yuan Wei Qing-Xia Peng Li-Fang Duan Wei Wang Hong Zhang 《Journal of cellular and molecular medicine》2021,25(4):2213-2227
The activation of pancreatic stellate cells (PSCs) plays a critical role in the progression of pancreatic fibrosis. Nuclear factor-kappa B ( NF-κB) is associated with chronic pancreatitis (CP). Previous evidence indicated that NF-κB in acinar cells played a double-edged role upon pancreatic injury, whereas NF-κB in inflammatory cells promoted the progression of CP. However, the effects of NF-κB in PSCs have not been studied. In the present study, using two CP models and RNAi strategy of p65 in cultured PSCs, we found that the macrophage infiltration and MCP-1 expression were increased, and the NF-κBp65 protein level was elevated. NF-κBp65 was co-expressed with PSCs. In vitro, TGF-β1 induced overexpression of the TGF-β receptor 1, phosphorylated TGF-β1–activated kinase 1 (p-TAK1) and NF-κB in the PSCs. Moreover, the concentration of MCP-1 in the supernatant of activated PSCs was elevated. The migration of BMDMs was promoted by the supernatant of activated PSCs. Further knockdown of NF-κBp65 in PSCs resulted in a decline of BMDM migration, accompanied by a lower production of MCP-1. These findings indicate that TGF-β1 can induce the activation of NF-κB pathway in PSCs by regulating p-TAK1, and the NF-κB pathway in PSCs may be a target of chronic inflammation and fibrosis. 相似文献
918.
Xiaoqing Wu Xiaorui Xie Linjuan Su Na Lin Bin Liang Nan Guo Qingquan Chen Liangpu Xu Hailong Huang 《Journal of cellular and molecular medicine》2021,25(18):8929-8935
Pallister-Killian syndrome (PKS) is a rare sporadic genetic disorder usually caused by mosaicism of an extra isochromosome of 12p (i(12p)). This retrospective study analysed the prenatal ultrasound manifestations and molecular and cytogenetic results of five PKS foetuses. Samples of amniotic fluid and/or cord blood, skin biopsy and placenta were collected. Conventional karyotyping and single nucleotide polymorphism array (SNP array) were performed on all the amniotic fluid or cord blood samples. Copy number variants sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were also used for the validation for one foetus. All the five foetuses were from pregnancies with advanced parental age. Two foetuses involved structural abnormalities and one foetus had only soft markers, all of which included increased nuchal translucency. The rest two foetuses had normal ultrasounds in the second trimester, which has rarely been reported before. The karyotype revealed typical i(12p) in four cases and a small supernumerary marker chromosome consisting of 12p and 20p in the remaining one case. The proportion of cells with i(12p) ranged from 0 to 100% in cultural cells, while SNP array results suggested 2−4 copies of 12p. For one foetus, metaphase FISH showed normal results, but the interphase FISH suggested cell lines with two, three and four copies of 12p in the amniotic fluid. Advanced parental age may be an important risk factor for PKS, and there were no typical ultrasound manifestations related to PKS. A combination of karyotype analysis and molecular diagnosis is an effective method for the diagnosis of PKS. 相似文献
919.
920.
Both Enterococcus faecalis and Escherichia coli can undergo abrupt temperature transitions in nature. E. coli changes the composition of its phospholipid acyl chains in response to shifts growth temperature. This is mediated by a naturally temperature sensitive enzyme, FabF (3-ketoacyl-acyl carrier protein synthase II), that elongates the 16 carbon unsaturated acyl chain palmitoleate to the 18 carbon unsaturated acyl chain, cis-vaccenate. FabF is more active at low temperatures resulting in increased incorporation of cis-vaccenoyl acyl chains into the membrane phospholipids. This response to temperature is an intrinsic property of FabF and does not require increased synthesis of the enzyme. We report that the FabF of the very divergent bacterium, E. faecalis, has properties very similar to E. coli FabF and is responsible for changing E. faecalis membrane phospholipid acyl chain composition in response to temperature. Moreover, expression E. faecalis FabF in an E. coli ∆fabF strain restores temperature regulation to the E. coli strain. 相似文献