全文获取类型
收费全文 | 39488篇 |
免费 | 3684篇 |
国内免费 | 5879篇 |
出版年
2024年 | 175篇 |
2023年 | 698篇 |
2022年 | 1438篇 |
2021年 | 2273篇 |
2020年 | 1661篇 |
2019年 | 2061篇 |
2018年 | 1830篇 |
2017年 | 1337篇 |
2016年 | 1755篇 |
2015年 | 2663篇 |
2014年 | 3232篇 |
2013年 | 3289篇 |
2012年 | 4039篇 |
2011年 | 3502篇 |
2010年 | 2322篇 |
2009年 | 2136篇 |
2008年 | 2351篇 |
2007年 | 2084篇 |
2006年 | 1779篇 |
2005年 | 1563篇 |
2004年 | 1313篇 |
2003年 | 1140篇 |
2002年 | 908篇 |
2001年 | 562篇 |
2000年 | 464篇 |
1999年 | 463篇 |
1998年 | 331篇 |
1997年 | 268篇 |
1996年 | 236篇 |
1995年 | 205篇 |
1994年 | 165篇 |
1993年 | 115篇 |
1992年 | 128篇 |
1991年 | 102篇 |
1990年 | 91篇 |
1989年 | 76篇 |
1988年 | 63篇 |
1987年 | 45篇 |
1986年 | 40篇 |
1985年 | 50篇 |
1984年 | 17篇 |
1983年 | 18篇 |
1982年 | 18篇 |
1981年 | 16篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1975年 | 3篇 |
1950年 | 4篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
21.
Mengmeng Zhuang Yuequ Deng Wenwen Zhang Bo Zhu Hao Yan Jiaqi Lou Pan Zhang Qingwei Cui Hao Tang Han Sun Yong Sun 《Cell death & disease》2021,12(6)
Intestinal mucosal injuries are directly or indirectly related to many common acute and chronic diseases. Long non-coding RNAs (lncRNAs) are expressed in many diseases, including intestinal mucosal injury. However, the relationship between lncRNAs and intestinal mucosal injury has not been determined. Here, we investigated the functions and mechanisms of action of lncRNA Bmp1 on damaged intestinal mucosa. We found that Bmp1 was increased in damaged intestinal mucosal tissue and Bmp1 overexpression was able to alleviate intestinal mucosal injury. Bmp1 overexpression was found to influence cell proliferation, colony formation, and migration in IEC-6 or HIEC-6 cells. Moreover, miR-128-3p was downregulated after Bmp1 overexpression, and upregulation of miR-128-3p reversed the effects of Bmp1 overexpression in IEC-6 cells. Phf6 was observed to be a target of miR-128-3p. Furthermore, PHF6 overexpression affected IEC-6 cells by activating PI3K/AKT signaling which was mediated by the miR-128-3p/PHF6 axis. In conclusion, Bmp1 was found to promote the expression of PHF6 through the sponge miR-128-3p, activating the PI3K/AKT signaling pathway to promote cell migration and proliferation.Subject terms: Cell growth, Cell migration 相似文献
22.
23.
Bioaccessibility measurements have the potential to improve the accuracy of risk assessments and reduce the potential costs of remediation when they reveal that the solubility of chemicals in a matrix (e.g., soil) differs markedly from that in the critical toxicity study (i.e., the key study from which a toxicological or toxicity reference value is derived). We aimed to apply this approach to a brownfield site contaminated with chromium, and found that the speciation was CrIII, using a combination of alkaline digestion/diphenylcarbazide complexation and X-ray absorption near edge structure analysis. The bioaccessibility of Cr2O3, the compound on which a reference dose for CrIII is based, was substantially lower (<0.1%) than that of the CrIII in the soils, which was a maximum of 9%, giving relative bioaccessibility values of 13,000% in soil. This shows that the reference dose is based on essentially an insoluble compound, and thus we suggest that other compounds be considered for toxicity testing and derivation of reference dose. Two possibilities are CrCl3·6H2O and KCr(SO4)2·12H2O, which have been used for derivation of ecological toxicity reference values and are soluble at a range of dosing levels in our bioaccessibility tests. 相似文献
24.
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
25.
We analyzed the pattern of correlations among fitness components, herbivory, and resin characteristics in a natural all-aged
stand of ponderosa pine, to infer the strength and mechanism of natural selection on plant chemistry. Male and female cone
production were monitored yearly for 15 years, and levels of herbivory for 9 years in 165 trees. Resin flow rate and monoterpene
composition were determined for these same trees. Multiple regression of fitness components on resin characteristics showed
significant associations consistent with directional selection for increased resin flow rates and increased proportions of
α- and β-pinene, myrcene and terpinolene. However, negative correlations among monoterpene fractions of the resin constrained
the overall selection. Selective herbivory by aphids approached statistical significance and monoterpenes showed some (non-significant)
effect as deterrents against deer browse. Resin characteristics were not correlated with attack by cone insects or porcupines.
However, the association between resin characteristics and fitness is significantly different from that predicted by the path
coefficients involving herbivores. Therefore the hypothesis that these herbivores mediate selection on the resin is not supported
by the observed pattern of correlations among resin characteristics, herbivory, growth and fecundity. In this population,
most of the association between resin characteristics and fitness appears to be mediated by some other factor independent
of attack by herbivore species present.
Received: 18 March 1996/Accepted: 18 July 1996 相似文献
26.
Antigen presenting cells (APCs) in skin can promote either antigen-specific effector functions or antigen tolerance, and thus determine clearance or persistence of cutaneous viral infections. Human papillomavirus (HPV) infections can persist in squamous epithelium in immunocompetent individuals, and some persisting HPV infections, particularly with HPV16, promote malignant epithelial transformation. Here, we investigate whether local expression of the HPV16 protein most associated with malignant transformation, HPV16-E7, affects the phenotype and function of APC subsets in the skin. We demonstrate an expanded population of Langerhans cells in HPV16-E7 transgenic skin with distinct cell surface markers which express immune-modulatory enzymes and cytokines not expressed by cells from non transgenic skin. Furthermore, HPV16-E7 transgene expression in keratinocytes attracts new APC subsets to the epidermis. In vivo migration and transport of antigen to the draining lymph node by these APCs is markedly enhanced in HPV16-E7 expressing skin, whereas antigen-processing, as measured by proteolytic cleavage of DQ-OVA and activation of T cells in vivo by APCs, is significantly impaired. These data suggest that local expression of HPV16-E7 in keratinocytes can contribute to persisting infection with this oncogenic virus, by altering the phenotype and function of local APCs. 相似文献
27.
Yao Chen Jie Zhu Jun Mo Hongyu Yang Xueyang Jiang Hongzhi Lin 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):290-302
Small molecule cholinesterases inhibitor (ChEI) provides an effective therapeutic strategy to treat Alzheimer’s disease (AD). Currently, the discovery of new ChEI with multi-target effect is still of great importance. Herein, we report the synthesis, structure–activity relationship study and biological evaluation of a series of tacrine-cinnamic acid hybrids as new ChEIs. All target compounds are evaluated for their in vitro cholinesterase inhibitory activities. The representatives which show potent activity on cholinesterase, are evaluated for the amyloid β-protein self-aggregation inhibition and in vivo assays. The optimal compound 19, 27, and 30 (human AChE IC50?=?10.2?±?1.2, 16.5?±?1.7, and 15.3?±?1.8?nM, respectively) show good performance in ameliorating the scopolamine-induced cognition impairment and preliminary safety in hepatotoxicity evaluation. These compounds deserve further evaluation for the development of new therapeutic agents against AD. 相似文献
28.
29.
Yunhe Meng Xixi Shao Yan Wang Yumei Li Xiaojian Zheng Gongyuan Wei Seon-Won Kim Chonglong Wang 《Biotechnology and bioengineering》2020,117(11):3499-3507
Squalene is a lipophilic and non-volatile triterpene with many industrial applications for food, pharmaceuticals, and cosmetics. Metabolic engineering focused on optimization of the production pathway suffer from little success in improving titers because of a limited space of the cell membrane accommodating the lipophilic product. Extension of cell membrane would be a promising approach to overcome the storage limitation for successful production of squalene. In this study, Escherichia coli was engineered for squalene production by overexpression of some membrane proteins. The highest production of 612 mg/L was observed in the engineered E. coli with overexpression of Tsr, a serine chemoreceptor protein, which induced invagination of inner membrane to form multilayered structure. It was also observed an increase in unsaturated fatty acid in membrane lipids composition, suggesting cellular response to maintain membrane fluidity against squalene accumulation in the engineered strain. This study potentiates the capability of E. coli for squalene production and provides an effective strategy for the enhanced production of such compounds. 相似文献
30.
Xin Deng Guoli Zhang Ling Zhang Yan Feng Zehong Li GuangMou Wu Yuhuan Yue Gensong Li Yu Cao Ping Zhu 《PloS one》2015,10(11)
Non-viral gene delivery system with many advantages has a great potential for the future of gene therapy. One inherent obstacle of such approach is the uptake by endocytosis into vesicular compartments. Receptor-mediated gene delivery method holds promise to overcome this obstacle. In this study, we developed a receptor-mediated gene delivery system based on a combination of the Pseudomonas exotoxin A (PE), which has a receptor binding and membrane translocation domain, and the hyperthermophilic archaeal histone (HPhA), which has the DNA binding ability. First, we constructed and expressed the rPE-HPhA fusion protein. We then examined the cytotoxicity and the DNA binding ability of rPE-HPhA. We further assessed the efficiency of transfection of the pEGF-C1 plasmid DNA to CHO cells by the rPE-HPhA system, in comparison to the cationic liposome method. The results showed that the transfection efficiency of rPE-HPhA was higher than that of cationic liposomes. In addition, the rPE-HPhA gene delivery system is non-specific to DNA sequence, topology or targeted cell type. Thus, the rPE-HPhA system can be used for delivering genes of interest into mammalian cells and has great potential to be applied for gene therapy. 相似文献