全文获取类型
收费全文 | 2813篇 |
免费 | 162篇 |
国内免费 | 4篇 |
出版年
2023年 | 9篇 |
2022年 | 16篇 |
2021年 | 36篇 |
2020年 | 30篇 |
2019年 | 47篇 |
2018年 | 70篇 |
2017年 | 46篇 |
2016年 | 76篇 |
2015年 | 131篇 |
2014年 | 152篇 |
2013年 | 193篇 |
2012年 | 248篇 |
2011年 | 246篇 |
2010年 | 161篇 |
2009年 | 121篇 |
2008年 | 193篇 |
2007年 | 192篇 |
2006年 | 132篇 |
2005年 | 148篇 |
2004年 | 156篇 |
2003年 | 85篇 |
2002年 | 87篇 |
2001年 | 70篇 |
2000年 | 74篇 |
1999年 | 59篇 |
1998年 | 15篇 |
1997年 | 16篇 |
1996年 | 16篇 |
1995年 | 21篇 |
1994年 | 10篇 |
1993年 | 7篇 |
1992年 | 16篇 |
1991年 | 20篇 |
1990年 | 10篇 |
1989年 | 8篇 |
1988年 | 8篇 |
1987年 | 9篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1984年 | 2篇 |
1980年 | 5篇 |
1979年 | 8篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1970年 | 1篇 |
1969年 | 4篇 |
1967年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有2979条查询结果,搜索用时 156 毫秒
71.
P2Y12 antagonist attenuates eosinophilic inflammation and airway hyperresponsiveness in a mouse model of asthma 下载免费PDF全文
Dong‐Hyeon Suh Hoang Kim Tu Trinh Jing‐Nan Liu Le Duy Pham Sang Myun Park Hae‐Sim Park Yoo Seob Shin 《Journal of cellular and molecular medicine》2016,20(2):333-341
Leukotriene E4 (LTE4) that plays a key role in airway inflammation is expressed on platelets and eosinophils. We investigated whether blocking of the P2Y12 receptor can suppress eosinophilic inflammation in a mouse model of asthma because platelets and eosinophils share this receptor to be activated. BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA), followed by OVA nebulization. On each challenge day, clopidogrel, a P2Y12 antagonist was administered 30 min. before each challenge. Forty‐eight hours after the last OVA challenge, mice were assessed for airway hyperresponsiveness (AHR), cell composition and cytokine levels, including chemokine ligand 5 (CCL5), in bronchoalveolar lavage (BAL) fluid. EOL cells were treated with LTE4, with or without clopidogrel treatment, and intracellular and extracellular eosinophil cationic protein (ECP) expressions were measured to find the inhibiting function of P2Y12 antagonist on eosinophilic activation. The levels of P2Y12 expression were increased markedly in the lung homogenates of OVA‐sensitized and ‐challenged mice after platelet depletion. Administration of clopidogrel decreased AHR and the number of airway inflammatory cells, including eosinophils, in BAL fluid following OVA challenge. These results were associated with decreased levels of Th2 cytokines and CCL5. Histological examination showed that inflammatory cells as well as mucus‐containing goblet cells were reduced in clopidogrel‐administered mice compared to vehicle‐treated mice. Clopidogrel inhibited extracellular ECP secretion after LTE4 stimulation in EOL‐1 cells. Clopidogrel could prevent development of AHR and airway inflammation in a mouse model of asthma. P2Y12 can be a novel therapeutic target to the suppression of eosinophils in asthma. 相似文献
72.
Seul-gi Lee Mihye Kim Cho Een Kim Jisu Kang Hyunji Yoo Sang Hyun Sung 《Bioscience, biotechnology, and biochemistry》2016,80(11):2080-2086
Siegesbeckia pubescens (Compositae) is an annual herb indigenous to Korean mountainous regions. Recent reports have been issued on some compounds derived from S. pubescens for its anti-inflammatory activity or mode of action. The quercetin 3,7-O-dimethyl ether (QDE) isolated from the herbs of S. pubescens suppressed the lipopolysaccharide (LPS)-induced nitric oxide and inducible nitric oxide synthase (iNOS) protein production in mouse macrophages. QDE downregulated pro-inflammatory cytokines such as interleukin (IL)-6, IL-1β, tumor necrosis factor -α levels in LPS-stimulated macrophages. Also, QDE decreased the expression of LPS-induced iNOS and cyclooxygenase-2 (COX-2) protein and the production of IL-8 in LPS-induced HT-29 cells. Macrophages and colon epithelial cells are important for regulating the colon immune systems, thus QDE may regulate inflammatory colon disease via LPS-induced inflammation in macrophages and colon epithelial cells. QDE, anti-inflammatory constituent of S. pubescens herbs, can be expected to be a potential candidate for therapeutics against inflammatory bowel disease. 相似文献
73.
E. S. Seong J. H. Yoo N. J. Kim J. H. Choi J. G. Lee B. K. Ghimire I. M. Chung C. Y. Yu 《Russian Journal of Plant Physiology》2016,63(1):124-131
The tomato bZIP2-encoding gene was inserted into the Nicotiana benthamiana genome using Agrobacterium-mediated transformation to characterize resistance to oxidative stress and two herbicides, glyphosate and paraquat. We produced transgenic tobacco plants using the LebZIP2 gene, which were then utilized to examine salt stress and herbicide resistance through oxidative mechanisms. Transgenic LebZIP2-overexpressing plants were examined using specific primers for selection marker genes (PCR using genomic DNA) and target genes (RT-PCR). Based on microscopic examination, we observed an increase in leaf thickness and cell number in transgenic plants. The electrolyte leakage of leaves suggested that LebZIP2-overexpressing lines were weak tolerant to NaCl stress and resistant to methyl viologen. During our analysis, transgenic lines were exposed to different herbicides. Transgenic plants showed an increased tolerance based on visual injury, as well as an increased biomass. Based on these results, the LebZIP2 gene may be involved in oxidative stress tolerance and cell development in plants. 相似文献
74.
Seon Woo A. An Eun‐Seok Choi Wooseon Hwang Heehwa G. Son Jae‐Seong Yang Keunhee Seo Hyun‐Jun Nam Nhung T. H. Nguyen Eun Ji E. Kim Bo Kyoung Suh Youngran Kim Shunji Nakano Youngjae Ryu Chang Man Ha Ikue Mori Sang Ki Park Joo‐Yeon Yoo Sanguk Kim Seung‐Jae V. Lee 《Aging cell》2019,18(3)
PDZ domain‐containing proteins (PDZ proteins) act as scaffolds for protein–protein interactions and are crucial for a variety of signal transduction processes. However, the role of PDZ proteins in organismal lifespan and aging remains poorly understood. Here, we demonstrate that KIN‐4, a PDZ domain‐containing microtubule‐associated serine‐threonine (MAST) protein kinase, is a key longevity factor acting through binding PTEN phosphatase in Caenorhabditis elegans. Through a targeted genetic screen for PDZ proteins, we find that kin‐4 is required for the long lifespan of daf‐2/insulin/IGF‐1 receptor mutants. We then show that neurons are crucial tissues for the longevity‐promoting role of kin‐4. We find that the PDZ domain of KIN‐4 binds PTEN, a key factor for the longevity of daf‐2 mutants. Moreover, the interaction between KIN‐4 and PTEN is essential for the extended lifespan of daf‐2 mutants. As many aspects of lifespan regulation in C. elegans are evolutionarily conserved, MAST family kinases may regulate aging and/or age‐related diseases in mammals through their interaction with PTEN. 相似文献
75.
76.
Yoo Jun-Il Shin In-Soo Jeon Jae-Gyu Yang Yeon-Mi Kim Jae-Gon Lee Dae-Woo 《Probiotics and antimicrobial proteins》2019,11(1):150-157
Probiotics and Antimicrobial Proteins - Although several studies have evaluated the inhibitory effect of probiotics on halitosis, findings are inconsistent. This systematic review and meta-analysis... 相似文献
77.
78.
The diphenyleneiodonium (DPI) is widely used as an inhibitor of flavoenzymes, particularly NADPH oxidase. In this study, we investigated the effect of DPI on the apoptosis of human RPE cells. DPI treatment in ARPE-19 cells evoked a dose- and time-dependent growth inhibition, and also induced DNA fragmentation and protein content of the proapoptotic factor Bax. In addition, DPI significantly induced the expression and phosphorylation of p53, which induces proapoptotic genes in response to DNA damage or irreparable cell cycle arrest. ROS have been implicated as a key factor in the activation of p53 by many chemotherapeutic drugs. Recent data on the regulation of intracellular ROS by DPI are controversial. Therefore, we analyzed whether DPI could contribute to the generation of intracellular ROS. Although there was increase in ROS level from cells treated for 24h with DPI, it was not detectable at early time points, required to induce p53 expression. And DPI-induced p53 expression was not affected by the ROS scavenger NAC. We conclude that DPI induces the expression of p53 by ROS-independent mechanism in ARPE-19 cells, and renders cells sensitive to drug-induced apoptosis by induction of p53 expression. 相似文献
79.
Arabidopsis mesophyll protoplasts: a versatile cell system for transient gene expression analysis 总被引:15,自引:0,他引:15
The transient gene expression system using Arabidopsis mesophyll protoplasts has proven an important and versatile tool for conducting cell-based experiments using molecular, cellular, biochemical, genetic, genomic and proteomic approaches to analyze the functions of diverse signaling pathways and cellular machineries. A well-established protocol that has been extensively tested and applied in numerous experiments is presented here. The method includes protoplast isolation, PEG-calcium transfection of plasmid DNA and protoplast culture. Physiological responses and high-throughput capability enable facile and cost-effective explorations as well as hypothesis-driven tests. The protoplast isolation and DNA transfection procedures take 6-8 h, and the results can be obtained in 2-24 h. The cell system offers reliable guidelines for further comprehensive analysis of complex regulatory mechanisms in whole-plant physiology, immunity, growth and development. 相似文献
80.
Pyrolysis mass spectrometry (PyMS) is a rapid, simple, high-resolution analytical method based on thermal degradation of complex
material in a vacuum, and has been widely applied to the discrimination of closely related microbial strains. Minimally prepared
samples of embryogenic and non-embryogenic calluses derived from various higher plants (sweet potato, morning glory, Korean
ginseng, Siberian ginseng, and balloon flower) were subjected to PyMS for spectral fingerprinting. A dendrogram based on the
unweighted pair group method, with arithmetic mean of pyrolysis mass spectra, divided the calluses into Siberian ginseng embryogenic
callus and the others, which were subsequently divided into embryogenic and non-embryogenic callus groups, regardless of plant
species from which the calluses were derived. In the non-embryogenic callus group, the dendrogram was in agreement with the
known taxonomy of the plants. These results indicate that PyMS analysis could be applied for discriminating plant calluses
based on embryogenic capacity and taxonomic classification. 相似文献