全文获取类型
收费全文 | 857篇 |
免费 | 55篇 |
专业分类
912篇 |
出版年
2024年 | 1篇 |
2023年 | 7篇 |
2022年 | 11篇 |
2021年 | 27篇 |
2020年 | 8篇 |
2019年 | 18篇 |
2018年 | 22篇 |
2017年 | 27篇 |
2016年 | 35篇 |
2015年 | 47篇 |
2014年 | 55篇 |
2013年 | 85篇 |
2012年 | 77篇 |
2011年 | 107篇 |
2010年 | 79篇 |
2009年 | 51篇 |
2008年 | 33篇 |
2007年 | 35篇 |
2006年 | 28篇 |
2005年 | 18篇 |
2004年 | 22篇 |
2003年 | 11篇 |
2002年 | 15篇 |
2001年 | 13篇 |
2000年 | 16篇 |
1999年 | 9篇 |
1998年 | 8篇 |
1997年 | 4篇 |
1996年 | 6篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 6篇 |
1991年 | 3篇 |
1990年 | 6篇 |
1989年 | 5篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有912条查询结果,搜索用时 15 毫秒
81.
Sthitapranjya Pati Ankit Sood Sourish Mukhopadhyay Vidita A Vaidya 《Journal of biosciences》2018,43(1):85-95
The medial prefrontal cortex (mPFC) is implicated in anxiety-like behaviour. In rodent models, perturbations of mPFC neuronal activity through pharmacological manipulations, optogenetic activation of mPFC neurons or cell-type specific pharmacogenetic inhibition of somatostatin interneurons indicate conflicting effects on anxiety-like behaviour. In the present study we examined the effects of pharmacogenetic activation of Ca2+/calmodulin-dependent protein kinase α (CamKIIα)-positive excitatory neurons on anxiety-like behaviour. We used clozapine-N-oxide (CNO) to pharmacogenetically activate virally delivered CamKIIα-hM3Dq-DREADD in mPFC excitatory neurons. The effects of acute CNO or vehicle treatment on anxiety-like behaviour in the open field and elevated plus maze tests were examined in rats virally infected with either CamKIIα-hM3Dq-DREADD or CamKIIα-GFP. In addition, the effects of acute CNO treatment on the expression of the neuronal activity marker c-Fos were examined in the mPFC as well as downstream target neuronal circuits using immunohistochemistry. Acute pharmacogenetic activation of mPFC excitatory neurons evoked a significant decrease in anxiety-like behaviour selectively on the elevated plus maze task, but not the open field test. Acute CNO treatment resulted in enhanced c-Fos-immunopositive cell number in the infralimbic, prelimbic and cingulate subdivisions of the mPFC. This was also accompanied by enhanced c-Fos-immunopositive cell number in multiple downstream circuits of the mPFC in CNO-treated hM3Dq animals. Acute pharmacogenetic activation of mPFC excitatory neurons reduces anxiety-like behaviour in a task-specific fashion accompanied by enhanced c-Fos expression in the mPFC and multiple target circuits implicated in the regulation of anxiety-like behaviour. 相似文献
82.
Pande Babita Parveen Noorshama Parganiha Arti Pati Atanu Kumar 《Sleep and biological rhythms》2018,16(4):431-439
Sleep and Biological Rhythms - We studied patterns in the distribution of chronotype and sleep–wake behavior in a randomly chosen sample population of Indian teenagers consisting 965... 相似文献
83.
Amrita Saxena Richa Raghuwanshi Harikesh Bahadur Singh 《Journal of Plant Growth Regulation》2016,35(2):377-389
Biocontrol strategies have been mainly focused on proposing the use of biocontrol agents (BCAs) isolated from the rhizospheric region of the plant for protection against phytopathogens. The present study evaluates the effectiveness of phyllospheric Trichoderma isolates in elevating the defense responses in chilli against Colletotrichum capsici infection and comparing its efficiency to the conventionally recommended rhizospheric Trichoderma strains. The elicitation of the defense network in the plants was analyzed using biochemical assays for important enzymes, that is, PAL, PO, PPO, TPC, SOD along with the total protein level in challenged plants over untreated and unchallenged control plants. The results recorded 2.1, 5.18, 3, 0.67, and 0.5-fold increases in TPC, PAL, PO, PPO, and total protein content in BHUF4 (phyllopsheric Trichoderma isolate)-treated plants when compared to control plants under C. capsici challenge. This was at par with the increment recorded in T16A (rhizospheric Trichoderma isolate)-treated chilli plants. The increment in growth parameters was also recorded after treatment with the isolated Trichoderma strains. Interestingly, the phyllospheric isolate (BHUF4) treatment recorded comparable growth promotion in chilli plants recording 36, 62, and 60 % increases in one of the major parameters of plant growth, that is, root length, no. of leaves, and dry weight, respectively. This study proposes the use of combined application of both rhizospheric as well as phyllospheric Trichoderma isolates for better and all around protection of plants against foliar as well as soil phytopathogens. This would be a novel approach in biological control strategy for better management of anthracnose disease of chilli. 相似文献
84.
85.
86.
Ashrafali M. Ismail Amrita Saha Ji S. Lee David F. Painter Yinghua Chen Gurdeep Singh Gabriela N. Condezo James Chodosh Carmen San Martín Jaya Rajaiya 《PLoS pathogens》2022,18(6)
As intracellular parasites, viruses exploit cellular proteins at every stage of infection. Adenovirus outbreaks are associated with severe acute respiratory illnesses and conjunctivitis, with no specific antiviral therapy available. An adenoviral vaccine based on human adenovirus species D (HAdV-D) is currently in use for COVID-19. Herein, we investigate host interactions of HAdV-D type 37 (HAdV-D37) protein IIIa (pIIIa), identified by affinity purification and mass spectrometry (AP-MS) screens. We demonstrate that viral pIIIa interacts with ubiquitin-specific protease 9x (USP9x) and Ran-binding protein 2 (RANBP2). USP9x binding did not invoke its signature deubiquitination function but rather deregulated pIIIa-RANBP2 interactions. In USP9x-knockout cells, viral genome replication and viral protein expression increased compared to wild type cells, supporting a host-favored mechanism for USP9x. Conversely, RANBP2-knock down reduced pIIIa transport to the nucleus, viral genome replication, and viral protein expression. Also, RANBP2-siRNA pretreated cells appeared to contain fewer mature viral particles. Transmission electron microscopy of USP9x-siRNA pretreated, virus-infected cells revealed larger than typical paracrystalline viral arrays. RANBP2-siRNA pretreatment led to the accumulation of defective assembly products at an early maturation stage. CRM1 nuclear export blockade by leptomycin B led to the retention of pIIIa within cell nuclei and hindered pIIIa-RANBP2 interactions. In-vitro binding analyses indicated that USP9x and RANBP2 bind to C-terminus of pIIIa amino acids 386–563 and 386–510, respectively. Surface plasmon resonance testing showed direct pIIIa interaction with recombinant USP9x and RANBP2 proteins, without competition. Using an alternative and genetically disparate adenovirus type (HAdV-C5), we show that the demonstrated pIIIa interaction is also important for a severe respiratory pathogen. Together, our results suggest that pIIIa hijacks RANBP2 for nuclear import and subsequent virion assembly. USP9x counteracts this interaction and negatively regulates virion synthesis. This analysis extends the scope of known adenovirus-host interactions and has potential implications in designing new antiviral therapeutics. 相似文献
87.
88.
Wayne Reeve Rui Tian Sofie De Meyer Vanessa Melino Jason Terpolilli Julie Ardley Ravi Tiwari John Howieson Ronald Yates Graham O’Hara Mohamed Ninawi Hazuki Teshima David Bruce Chris Detter Roxanne Tapia Cliff Han Chia-Lin Wei Marcel Huntemann James Han I-Min Chen Konstantinos Mavromatis Victor Markowitz Natalia Ivanova Galina Ovchinnikova Ioanna Pagani Amrita Pati Lynne Goodwin Sam Pitluck Tanja Woyke Nikos Kyrpides 《Standards in genomic sciences》2013,9(2):243-253
Rhizobium leguminosarum bv. trifolii strain TA1 is an aerobic, motile, Gram-negative, non-spore-forming rod that is an effective nitrogen fixing microsymbiont on the perennial clovers originating from Europe and the Mediterranean basin. TA1 however is ineffective with many annual and perennial clovers originating from Africa and America. Here we describe the features of R. leguminosarum bv. trifolii strain TA1, together with genome sequence information and annotation. The 8,618,824 bp high-quality-draft genome is arranged in a 6 scaffold of 32 contigs, contains 8,493 protein-coding genes and 83 RNA-only encoding genes, and is one of 20 rhizobial genomes sequenced as part of the DOE Joint Genome Institute 2010 Community Sequencing Program. 相似文献
89.
Pati S Lee Y Samaniego F 《Apoptosis : an international journal on programmed cell death》2000,5(1):21-28
Analysis of the protein composition of urine has been the subject of much research that has captured the interest of scientific groups over the years. A number of factors have been isolated from urine that possess anti-neoplastic activities as seen both in vitro and in vivo studies. The urine from pregnant women and commercial preparations of crude clinical grade human chorionic gonadotropin contain factors (HAF for hCG associated factor) with anti-Kaposi's sarcoma activity. Also found in urine with activity are eosinophil-derived neurotoxin (EDN), anti-neoplastic urinary protein (ANUP), inhibin, activin A, and angiostatin. The anti-cancer activity of urinary proteins is associated with apoptosis of endothelial cells and of tumor-associated endothelial cells. A better understanding of the biological functions of these various urinary proteins, and of others that remain to be discovered, should provide insights into novel cell regulatory systems operating during pregnancy. 相似文献
90.
Amrita Datta Chaudhuri Savan Kabaria Doo Chul Choi M. Maral Mouradian Eunsung Junn 《The Journal of biological chemistry》2015,290(19):12425-12434
Parkinson disease is associated with decreased activity of the mitochondrial electron transport chain. This defect can be recapitulated in vitro by challenging dopaminergic cells with 1-methyl-4-phenylpyridinium (MPP+), a neurotoxin that inhibits complex I of electron transport chain. Consequently, oxidative phosphorylation is blocked, and cells become dependent on glycolysis for ATP production. Therefore, increasing the rate of glycolysis might help cells to produce more ATP to meet their energy demands. In the present study, we show that microRNA-7, a non-coding RNA that protects dopaminergic neuronal cells against MPP+-induced cell death, promotes glycolysis in dopaminergic SH-SY5Y and differentiated human neural progenitor ReNcell VM cells, as evidenced by increased ATP production, glucose consumption, and lactic acid production. Through a series of experiments, we demonstrate that targeted repression of RelA by microRNA-7, as well as subsequent increase in the neuronal glucose transporter 3 (Glut3), underlies this glycolysis-promoting effect. Consistently, silencing Glut3 expression diminishes the protective effect of microRNA-7 against MPP+. Further, microRNA-7 fails to prevent MPP+-induced cell death when SH-SY5Y cells are cultured in a low glucose medium, as well as when differentiated ReNcell VM cells or primary mouse neurons are treated with the hexokinase inhibitor, 2-deoxy-d-glucose, indicating that a functional glycolytic pathway is required for this protective effect. In conclusion, microRNA-7, by down-regulating RelA, augments Glut3 expression, promotes glycolysis, and subsequently prevents MPP+-induced cell death. This protective effect of microRNA-7 could be exploited to correct the defects in oxidative phosphorylation in Parkinson disease. 相似文献