全文获取类型
收费全文 | 2451篇 |
免费 | 166篇 |
国内免费 | 1篇 |
专业分类
2618篇 |
出版年
2023年 | 10篇 |
2022年 | 38篇 |
2021年 | 46篇 |
2020年 | 25篇 |
2019年 | 41篇 |
2018年 | 43篇 |
2017年 | 49篇 |
2016年 | 61篇 |
2015年 | 110篇 |
2014年 | 141篇 |
2013年 | 151篇 |
2012年 | 223篇 |
2011年 | 194篇 |
2010年 | 139篇 |
2009年 | 104篇 |
2008年 | 148篇 |
2007年 | 116篇 |
2006年 | 131篇 |
2005年 | 138篇 |
2004年 | 122篇 |
2003年 | 107篇 |
2002年 | 77篇 |
2001年 | 56篇 |
2000年 | 79篇 |
1999年 | 44篇 |
1998年 | 21篇 |
1997年 | 14篇 |
1996年 | 9篇 |
1995年 | 10篇 |
1994年 | 7篇 |
1993年 | 17篇 |
1992年 | 19篇 |
1991年 | 15篇 |
1990年 | 12篇 |
1989年 | 9篇 |
1988年 | 12篇 |
1987年 | 6篇 |
1986年 | 3篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1983年 | 9篇 |
1982年 | 10篇 |
1981年 | 3篇 |
1980年 | 8篇 |
1979年 | 12篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1974年 | 2篇 |
1971年 | 2篇 |
1969年 | 2篇 |
排序方式: 共有2618条查询结果,搜索用时 15 毫秒
71.
doi: 10.1111/j.1741‐2358.2011.00506.x Colonisation of the oral cavity by periodontopathic bacteria in complete denture wearers Objective: The purpose of this study was to investigate colonisation by periodontopathic bacteria and the sites of colonisation in elderly upper and lower complete denture wearers. We also investigated the relationship between level of oral hygiene and colonisation by periodontopathic bacteria. Materials and methods: Forty edentulous and 37 dentate volunteers participated in this study. Samples were collected from whole saliva, and levels of Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum were determined by PCR Invader technology. Detection of these species on oral mucosal and denture surfaces was performed by PCR. Fisher’s exact test was used for the statistical analysis. Cluster analysis was employed to investigate trends in the periodontopathic bacteria flora in each sampling area. Results: Detection rates of periodontopathic bacteria in whole saliva were lower under edentulous conditions than under dentulous conditions, except for A. actinomycetemcomitans and F. nucleatum (p < 0.01). Detection rate of F. nucleatum was the highest in all areas. A positive correlation was observed between DNA quantification of P. gingivalis and number of Candida species in saliva. Cluster analysis of the test species identified two clusters. Tongue‐coating status was associated with the detection rate of all periodontopathic bacteria investigated, and denture plaque status was associated with the detection rate of T. denticola and F. nucleatum. Conclusion: Results indicate the presence of periodontopathic bacteria under edentulous conditions and that the status of oral hygiene of the mucosal or denture surfaces affects colonisation by T. denticola and F. nucleatum. 相似文献
72.
Zhang T Berrocal JG Yao J DuMond ME Krishnakumar R Ruhl DD Ryu KW Gamble MJ Kraus WL 《The Journal of biological chemistry》2012,287(15):12405-12416
NMNAT-1 and PARP-1, two key enzymes in the NAD(+) metabolic pathway, localize to the nucleus where integration of their enzymatic activities has the potential to control a variety of nuclear processes. Using a variety of biochemical, molecular, cell-based, and genomic assays, we show that NMNAT-1 and PARP-1 physically and functionally interact at target gene promoters in MCF-7 cells. Specifically, we show that PARP-1 recruits NMNAT-1 to promoters where it produces NAD(+) to support PARP-1 catalytic activity, but also enhances the enzymatic activity of PARP-1 independently of NAD(+) production. Furthermore, using two-photon excitation microscopy, we show that NMNAT-1 catalyzes the production of NAD(+) in a nuclear pool that may be distinct from other cellular compartments. In expression microarray experiments, depletion of NMNAT-1 or PARP-1 alters the expression of about 200 protein-coding genes each, with about 10% overlap between the two gene sets. NMNAT-1 enzymatic activity is required for PARP-1-dependent poly(ADP-ribosyl)ation at the promoters of commonly regulated target genes, as well as the expression of those target genes. Collectively, our studies link the enzymatic activities of NMNAT-1 and PARP-1 to the regulation of a set of common target genes through functional interactions at target gene promoters. 相似文献
73.
In contrast to gene-for-gene disease resistance, nonhost resistance governs defense responses to a broad range of potential pathogen species. To identify specific genes involved in the signal transduction cascade associated with nonhost disease resistance, we used a virus-induced gene-silencing screen in Nicotiana benthamiana, and identified the peroxisomal enzyme glycolate oxidase (GOX) as an essential component of nonhost resistance. GOX-silenced N. benthamiana and Arabidopsis thaliana GOX T-DNA insertion mutants are compromised for nonhost resistance. Moreover, Arabidopsis gox mutants have lower H(2)O(2) accumulation, reduced callose deposition, and reduced electrolyte leakage upon inoculation with hypersensitive response-causing nonhost pathogens. Arabidopsis gox mutants were not affected in NADPH oxidase activity, and silencing of a gene encoding NADPH oxidase (Respiratory burst oxidase homolog) in the gox mutants did not further increase susceptibility to nonhost pathogens, suggesting that GOX functions independently from NADPH oxidase. In the two gox mutants examined (haox2 and gox3), the expression of several defense-related genes upon nonhost pathogen inoculation was decreased compared with wild-type plants. Here we show that GOX is an alternative source for the production of H(2)O(2) during both gene-for-gene and nonhost resistance responses. 相似文献
74.
Eun Kyung Jang Won Gu Kim Ho-Cheol Kim Jin-Won Huh Hyemi Kwon Yun Mi Choi Min Ji Jeon Tae Yong Kim Young Kee Shong Jin-Sook Ryu Won Bae Kim 《PloS one》2015,10(4)
ObjectivePulmonary function test (PFT) is a useful tool for an objective assessment of respiratory function. Impaired pulmonary function is critical for the survival and quality of life in patients with pulmonary metastases of solid cancers including thyroid cancer. This study aimed to evaluate clinical factors associated with severely impaired pulmonary function by serial assessment with PFT in patients with pulmonary metastasis of differentiated thyroid cancer (DTC) who received radioactive iodine treatment (RAIT).PatientsThis retrospective study enrolled 31 patients who underwent serial PFTs before and after RAIT for pulmonary metastasis of DTC. We evaluated the risk factors for severe impairment of pulmonary function.ResultsThe median age of the patients was 44.1 years and 18 of them were female patients. Severe impairment of pulmonary function was observed in five patients (16%) after a median of three RAITs (cumulative I-131 activity = 20.4 GBq). These patients were older and more frequently had mild impairment of baseline pulmonary function, respiratory symptoms, or progressive disease compared with patients with stable pulmonary function. Neither cumulative dose nor number of RAIT was associated with decreased pulmonary function. Coexisting pulmonary diseases, presence of respiratory symptoms, and metastatic disease progression were significantly associated with severe decrease in forced vital capacity during follow-up (p =.047, p =.011, and p =.021, respectively).ConclusionsPulmonary function was severely impaired during follow-up in some patients with pulmonary metastasis of DTC after a high-dose RAITs. Neither the number of RAIT nor the cumulative I-131 activity was associated with decreased pulmonary function. Serial PFT might be considered for some high-risk patients during follow-up. 相似文献
75.
Umata T Hirata M Takahashi T Ryu F Shida S Takahashi Y Tsuneoka M Miura Y Masuda M Horiguchi Y Mekada E 《The Journal of biological chemistry》2001,276(32):30475-30482
Ectodomain shedding is an important mechanism to regulate the biological activities of membrane proteins. We focus here on the signaling mechanism of the ectodomain shedding of heparin-binding epidermal growth factor (EGF)-like growth factor (pro HB-EGF). Lysophosphatidic acid (LPA), a ligand for seven-transmembrane G protein-coupled receptors, stimulates the shedding of pro HB-EGF, which constitutes a G protein-coupled receptor-mediated transactivation of the EGF receptor. Experiments using a series of inhibitors and overexpression of mutant forms of signaling molecules revealed that the Ras-Raf-MEK signal is essential for the LPA-induced shedding. In addition, the small GTPase Rac is involved in the LPA-induced shedding, possibly to promote MEK activation. 12-O-Tetradecanoylphorbol-13-acetate is another potent inducer of pro HB-EGF shedding. We also demonstrate that the LPA-induced pathway is distinct from the 12-O-tetradecanoylphorbol-13-acetate-induced pathway and that these pathways constitute a dual signaling cascade that regulates the shedding of pro HB-EGF. 相似文献
76.
Aims: The objective of this study was to inactivate Bacillus cereus spores in sikhye using a modified tyndallization process involving injection with carbon dioxide (CO2). Methods and Results: Heat tolerance of B. cereus spores in tryptic soy broth and sikhye was evaluated. The D95°C values of the B. cereus spores were 2·8–4·9 min, dependent of type of heating medium or inoculum level. The lethality of conventional heat treatment and modified tyndallization with or without CO2 injection against B. cereus spores in sikhye was determined. The order of effectiveness was modified tyndallization with CO2 > modified tyndallization without CO2 > conventional heat treatment. Modified tyndallization with CO2 reduced the number of B. cereus spores in sikhye by 5·8 log CFU ml?1. The increased CO2 concentration and decreased pH of sikhye resulting from CO2 injection rapidly reverted to near‐normal values after heat treatment. Conclusions: Modified tyndallization with CO2 was more effective than conventional heat treatment or modified tyndallization without CO2 in reducing B. cereus spores in sikhye. Significance and Impact of the Study: Results of this study will be useful when developing strategies to control B. cereus spores in sikhye and may have application to other beverages. 相似文献
77.
78.
Dual requirement for rho and protein kinase C in direct activation of phospholipase D1 through G protein-coupled receptor signaling 总被引:2,自引:0,他引:2 下载免费PDF全文
Du G Altshuller YM Kim Y Han JM Ryu SH Morris AJ Frohman MA 《Molecular biology of the cell》2000,11(12):4359-4368
G protein-coupled and tyrosine kinase receptor activation of phospholipase D1 (PLD1) play key roles in agonist-stimulated cellular responses such as regulated exocytosis, actin stress fiber formation, and alterations in cell morphology and motility. Protein Kinase C, ADP-ribosylation factor (ARF), and Rho family members activate PLD1 in vitro; however, the actions of the stimulators on PLD1 in vivo have been proposed to take place through indirect pathways. We have used the yeast split-hybrid system to generate PLD1 alleles that fail to bind to or to be activated by RhoA but that retain wild-type responses to ARF and PKC. These alleles then were employed in combination with alleles unresponsive to PKC or to both stimulators to examine the activation of PLD1 by G protein-coupled receptors. Our results demonstrate that direct stimulation of PLD1 in vivo by RhoA (and by PKC) is critical for significant PLD1 activation but that PLD1 subcellular localization and regulated phosphorylation occur independently of these stimulatory pathways. 相似文献
79.
In yeast, trehalose-6-phosphate synthase is a key enzyme for trehalose biosynthesis, encoded by the structural gene TPS1. Trehalose affects sugar metabolism as well as osmoprotection against several environmental stresses, such as heat and desiccation. The TPS1 gene of Saccharomyces cerevisiae was engineered under the control of the CaMV 35S promoter for constitutive expression in transgenic potato plants by Ti-plasmid of Agrobacterium-mediated transformation. The resulting TPS1 transgenic potato plants exhibited various morphological phenotypes in culture tubes, ranging from normal to severely retarded growth, including dwarfish growth, yellowish lancet-shaped leaves, and aberrant root development. However, the plants recovered from these negative growth effects when grown in a soil mixture. The TPS1 transgenic potato plants showed significantly increased drought resistance. These results suggest that the production of trehalose not only affects plant development but also improves drought tolerance. 相似文献
80.
Ganipisetti Srinivasrao Jung-Eun Park Sungmin Kim Mija Ahn Chaejoon Cheong Ky-Youb Nam Pethaiah Gunasekaran Eunha Hwang Nam-Hyung Kim Song Yub Shin Kyung S. Lee Eunkyung Ryu Jeong Kyu Bang 《PloS one》2014,9(9)