全文获取类型
收费全文 | 108009篇 |
免费 | 8384篇 |
国内免费 | 9027篇 |
专业分类
125420篇 |
出版年
2024年 | 240篇 |
2023年 | 1417篇 |
2022年 | 3260篇 |
2021年 | 5511篇 |
2020年 | 3777篇 |
2019年 | 4679篇 |
2018年 | 4428篇 |
2017年 | 3238篇 |
2016年 | 4591篇 |
2015年 | 6676篇 |
2014年 | 7844篇 |
2013年 | 8297篇 |
2012年 | 9979篇 |
2011年 | 8974篇 |
2010年 | 5545篇 |
2009年 | 4971篇 |
2008年 | 5710篇 |
2007年 | 5130篇 |
2006年 | 4454篇 |
2005年 | 3492篇 |
2004年 | 2968篇 |
2003年 | 2719篇 |
2002年 | 2272篇 |
2001年 | 1866篇 |
2000年 | 1694篇 |
1999年 | 1669篇 |
1998年 | 1039篇 |
1997年 | 1001篇 |
1996年 | 941篇 |
1995年 | 821篇 |
1994年 | 789篇 |
1993年 | 617篇 |
1992年 | 818篇 |
1991年 | 617篇 |
1990年 | 466篇 |
1989年 | 443篇 |
1988年 | 354篇 |
1987年 | 344篇 |
1986年 | 266篇 |
1985年 | 286篇 |
1984年 | 156篇 |
1983年 | 161篇 |
1982年 | 99篇 |
1981年 | 85篇 |
1980年 | 60篇 |
1979年 | 77篇 |
1977年 | 59篇 |
1975年 | 56篇 |
1974年 | 52篇 |
1973年 | 56篇 |
排序方式: 共有10000条查询结果,搜索用时 14 毫秒
991.
Julia Li Zhong Chintan Raval Gavin P. Edwards Rex M. Tyrrell 《Free radical biology & medicine》2010,48(2):196-206
Ultraviolet A (UVA) radiation is an oxidizing agent that strongly induces the heme oxygenase 1 (HO-1) gene and expression of the protein in cultured human skin fibroblasts but weakly induces it in skin keratinocytes. Lower basal levels of HO-1 and much higher basal levels of HO-2 protein are observed in keratinocytes compared with fibroblasts. Using both overexpression and knockdown approaches, we demonstrate that HO-2 modulates basal and UVA-induced HO-1 protein levels, whereas HO-1 levels do not affect HO-2 levels in skin fibroblasts and keratinocytes. Silencing of Bach1 strongly increases HO-1 levels in transformed HaCaT keratinocytes and these HO-1 levels are not further increased by either UVA irradiation or silencing of HO-2. This is consistent with the conclusion that high constitutive levels of HO-2 expression in keratinocytes are responsible for the resistance of these cells to HO-1 induction by UVA radiation and that Bach1 plays a predominant role in influencing the lack of HO-1 expression in keratinocytes. Bach1 inhibition leading to HO-1 induction reduced UVA-irradiation-induced damage as monitored both by the extent of LDH release and by nuclear condensation, so that Bach1 inhibition seems to protect against UVA-irradiation-induced damage in keratinocytes. 相似文献
992.
Yaoquan Liu Yong Li David C. Myles Mark Claypool Christopher W. Carreras Simon J. Shaw 《Bioorganic & medicinal chemistry》2010,18(21):7651-7658
A series of derivatives of the amine of 9-dihydro-9-O-ethylamino-N-desmethyl-N-isopropyl erythromycin A derivatives were synthesized as motilin agonists. The compounds were developed for potency without showing antibacterial activity and inhibition of the hERG potassium channel. The formamide of the amide series was found to show the optimal combination of properties relative to carbamates, ureas, thioureas, and amines. This prompted an investigation of heterocyclic isosteres for the amide. In this series the triazole had the optimal combination of properties. From the study, two compounds met the criteria for detailed pharmacokinetic studies. 相似文献
993.
N. P. Markwick T. R. Glare C. Hauxwell Z. Li J. Poulton J. M. Ward V. L. Young V. K. Ward 《Journal of Applied Entomology》2010,134(1):61-71
The painted apple moth (PAM), Teia anartoides (Walker) (Lepidoptera: Lymantriidae) made a recent incursion into New Zealand. A nucleopolyhedrovirus (NPV), Orgyia anartoides NPV (OranNPV), originally isolated from PAM in Australia, was tested for its pathogenicity to PAM and a range of non‐target insect species found in New Zealand, to evaluate its suitability as a microbial control for this insect invader. Dosage‐mortality tests showed that OranNPV was highly pathogenic to PAM larvae; mean LT50 values for third instars ranged from 17.9 to 8.1 days for doses from 102 to 105 polyhedral inclusion bodies/larva, respectively. The cause of death in infected insects was confirmed as OranNPV. Molecular analysis established that OranNPV can be identified by PCR and restriction digestion, and this process complemented microscopic examination of infected larvae. No lymantriid species occur in New Zealand; however, the virus had no significant effects on species from five other lepidopteran families (Noctuidae, Tortricidae, Geometridae, Nymphalidae and Plutellidae) or on adult honeybees. Thus, all indications from this initial investigation are that OranNPV would be an important tool in the control of PAM in a future incursion of this species into New Zealand. 相似文献
994.
Zhihui Feng Zhongbo Liu Xuesen Li Haiqun Jia Lijuan Sun Chuan Tian Lihong Jia Jiankang Liu 《The Journal of nutritional biochemistry》2010,21(12):1222-1231
Vitamin E has long been identified as a major lipid-soluble chain-breaking antioxidant in mammals. α-Tocopherol is a vitamin E component and the major form in the human body. We propose that, besides its direct chain-breaking antioxidant activity, α-tocopherol may exert an indirect antioxidant activity by enhancing the cell's antioxidant system as a Phase II enzyme inducer. We investigated α-tocopherol's inducing effect on Phase II enzymes and its protective effect on acrolein-induced toxicity in a human retinal pigment epithelial (RPE) cell line, ARPE-19. Acrolein, a major component of cigarette smoke and also a product of lipid peroxidation, at 75 μmol/L over 24 h, caused significant loss of ARPE-19 cell viability, increased oxidative damage, decreased antioxidant defense, inactivation of the Keap1/Nrf2 pathway, and mitochondrial dysfunction. ARPE-19 cells have been used as a model of smoking- and age-related macular degeneration. Pretreatment with α-tocopherol activated the Keap1/Nrf2 pathway by increasing Nrf2 expression and inducing its translocation to the nucleus. Consequently, the expression and/or activity of the following Phase II enzymes increased: glutamate cysteine ligase, NAD(P)H:quinone oxidoreductase 1, heme-oxygenase 1, glutathione S-transferase and superoxide dismutase; total antioxidant capacity and glutathione also increased. This antioxidant defense enhancement protected ARPE-19 cells from an acrolein-induced decrease in cell viability, lowered reactive oxygen species and protein oxidation levels, and improved mitochondrial function. These results suggest that α-tocopherol protects ARPE-19 cells from acrolein-induced cellular toxicity, not only as a chain-breaking antioxidant, but also as a Phase II enzyme inducer. 相似文献
995.
996.
Hui Liu Xiang Li Matthew D. Dun Sam Faulkner Chen Chen Jiang Hubert Hondermarck 《Proteomics》2020,20(10)
Pancreatic cancer has a dismal prognosis and to date there are no targeted therapies for this malignancy. Using shotgun proteomics, the mRNA binding protein cold shock domain containing E1 (CSDE1), also called upstream‐of‐N‐Ras, is detected in pancreatic cancer cell lines but not in normal pancreatic epithelial cells. The expression of CSDE1 in pancreatic cancer cells is confirmed by Western blotting and immunohistochemistry of human pancreatic tumors. In vitro functional assays show that siRNA downregulation of CSDE1 or gene knockout using CRISPR‐Cas9 significantly reduce the invasiveness of pancreatic cancer cells. Together, this study reveals that CSDE1 is overexpressed in pancreatic cancer and is a potential therapeutic target to inhibit pancreatic cancer cell invasion. 相似文献
997.
Yidi Sun Chen Li Shichao Pang Qianlan Yao Luonan Chen Yixue Li Rong Zeng 《基因组蛋白质组与生物信息学报(英文版)》2020,18(5):525-538
The estrogen receptor (ER)-negative breast cancer subtype is aggressive with few treatment options available. To identify specific prognostic factors for ER-negative breast cancer, this study included 705,729 and 1034 breast invasive cancer patients from the Surveillance, Epidemiology, and End Results (SEER) and The Cancer Genome Atlas (TCGA) databases, respectively. To identify key differential kinase–substrate node and edge biomarkers between ER-negative and ER-positive breast cancer patients, we adopted a network-based method using correlation coefficients between molecular pairs in the kinase regulatory network. Integrated analysis of the clinical and molecular data revealed the significant prognostic power of kinase–substrate node and edge features for both subtypes of breast cancer. Two promising kinase–substrate edge features, CSNK1A1–NFATC3 and SRC–OCLN, were identified for more accurate prognostic prediction in ER-negative breast cancer patients. 相似文献
998.
The micropore structure is prerequisite for fast and durable endothelialization of artificial small diameter blood vessels (ASDBVs). Although some methods, such as salt leaching, coagulation, and electrospinning, have been developed to construct micropores for ASDBVs, the uncontrollability of the structure and the complicated procedures of the process are still the issues to be concerned about. In this study, a compact device based on the principle of centrifugal force is established and used to prepare polyurethane (PU) ASDBVs with micropore structures by blasting different porogens. It is found that the glass beads could construct micropores with regular round shape, uniform distribution, and controllable size (60–350 µm), which significantly improves the endothelialization of PU‐based ASDBVs, especially when the pore size is about 60 µm. This method is easy‐accessible and wide‐applicable, which provides a new pathway for the research and development of ASDBVs. 相似文献
999.
Guocai Yao Wenliang Zhang Minglei Yang Huan Yang Jianbo Wang Haiyue Zhang Lai Wei Zhi Xie Weizhong Li 《基因组蛋白质组与生物信息学报(英文版)》2020,18(6):760-772
Microbes play important roles in human health and disease. The interaction between microbes and hosts is a reciprocal relationship, which remains largely under-explored. Current computational resources lack manually and consistently curated data to connect metagenomic data to pathogenic microbes, microbial core genes, and disease phenotypes. We developed the MicroPhenoDB database by manually curating and consistently integrating microbe-disease association data. MicroPhenoDB provides 5677 non-redundant associations between 1781 microbes and 542 human disease phenotypes across more than 22 human body sites. MicroPhenoDB also provides 696,934 relationships between 27,277 unique clade-specific core genes and 685 microbes. Disease phenotypes are classified and described using the Experimental Factor Ontology (EFO). A refined score model was developed to prioritize the associations based on evidential metrics. The sequence search option in MicroPhenoDB enables rapid identification of existing pathogenic microbes in samples without running the usual metagenomic data processing and assembly. MicroPhenoDB offers data browsing, searching, and visualization through user-friendly web interfaces and web service application programming interfaces. MicroPhenoDB is the first database platform to detail the relationships between pathogenic microbes, core genes, and disease phenotypes. It will accelerate metagenomic data analysis and assist studies in decoding microbes related to human diseases. MicroPhenoDB is available through http://www.liwzlab.cn/microphenodb and http://lilab2.sysu.edu.cn/microphenodb. 相似文献
1000.
Zipeng Yu Yang Xu Lifei Zhu Lei Zhang Lin Liu Di Zhang Dandan Li Changai Wu Jinguang Huang Guodong Yang Kang Yan Shizhong Zhang Chengchao Zheng 《植物学报(英文版)》2020,62(4):403-420
Low molecular weight secreted peptides have recently been shown to affect multiple aspects of plant growth, development, and defense responses.Here, we performed stepwise BLAST filtering to identify unannotated peptides from the Arabidopsis thaliana protein database and uncovered a novel secreted peptide family, secreted transmembrane peptides(STMPs). These low molecular weight peptides, which consist of an N-terminal signal peptide and a transmembrane domain, were primarily localized to extracellular compartments but were also detected in the endomembrane system of the secretory pathway, including the endoplasmic reticulum and Golgi. Comprehensive bioinformatics analysis identified 10 STMP family members that are specific to the Brassicaceae family. Brassicaceae plants showed dramatically inhibited root growth uponexposure to chemically synthesized STMP1 and STMP2.Arabidopsis overexpressing STMP1, 2, 4, 6, or 10 exhibited severely arrested growth, suggesting that STMPs are involved in regulating plant growth and development. In addition, in vitro bioassays demonstrated that STMP1,STMP2, and STMP10 have antibacterial effects against Pseudomonas syringae pv. tomato DC3000, Ralstonia solanacearum, Bacillus subtilis, and Agrobacterium tumefaciens, demonstrating that STMPs are antimicrobial peptides. These findings suggest that STMP family members play important roles in various developmental events and pathogen defense responses in Brassicaceae plants. 相似文献