全文获取类型
收费全文 | 221篇 |
免费 | 22篇 |
出版年
2022年 | 1篇 |
2021年 | 2篇 |
2020年 | 2篇 |
2019年 | 5篇 |
2018年 | 3篇 |
2017年 | 5篇 |
2016年 | 5篇 |
2015年 | 12篇 |
2014年 | 6篇 |
2013年 | 19篇 |
2012年 | 15篇 |
2011年 | 17篇 |
2010年 | 6篇 |
2009年 | 7篇 |
2008年 | 13篇 |
2007年 | 13篇 |
2006年 | 13篇 |
2005年 | 14篇 |
2004年 | 22篇 |
2003年 | 7篇 |
2002年 | 12篇 |
2000年 | 5篇 |
1999年 | 1篇 |
1997年 | 4篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1984年 | 1篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1976年 | 2篇 |
排序方式: 共有243条查询结果,搜索用时 15 毫秒
101.
Shetty S Weston CJ Oo YH Westerlund N Stamataki Z Youster J Hubscher SG Salmi M Jalkanen S Lalor PF Adams DH 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(7):4147-4155
The common lymphatic endothelial and vascular endothelial receptor (CLEVER-1; also known as FEEL-1 and stabilin-1) is a recycling and intracellular trafficking receptor with multifunctional properties. In this study, we demonstrate increased endothelial expression of CLEVER-1/stabilin-1 at sites of leukocyte recruitment to the inflamed human liver including sinusoids, septal vessels, and lymphoid follicles in inflammatory liver disease and tumor-associated vessels in hepatocellular carcinoma. We used primary cultures of human hepatic sinusoidal endothelial cells (HSEC) to demonstrate that CLEVER-1/stabilin-1 expression is enhanced by hepatocyte growth factor but not by classical proinflammatory cytokines. We then showed that CLEVER-1/stabilin-1 supports T cell transendothelial migration across HSEC under conditions of flow with strong preferential activity for CD4 FoxP3(+) regulatory T cells (Tregs). CLEVER-1/stabilin-1 inhibition reduced Treg transendothelial migration by 40% and when combined with blockade of ICAM-1 and vascular adhesion protein-1 (VAP-1) reduced it by >80%. Confocal microscopy demonstrated that 60% of transmigrating Tregs underwent transcellular migration through HSEC via ICAM-1- and VAP-1-rich transcellular pores in close association with CLEVER-1/stabilin-1. Thus, CLEVER-1/stabilin-1 and VAP-1 may provide an organ-specific signal for Treg recruitment to the inflamed liver and to hepatocellular carcinoma. 相似文献
102.
Lehtinen M Pelttari E Elo H 《Zeitschrift für Naturforschung. C, Journal of biosciences》2011,66(11-12):562-570
We report the antimicrobial activity of formylchromones. These compounds are remote structural analogues of nalidixic acid and quinolone antibiotics, and their activity was investigated by a simple micro-scale method designed for the determination of minimal inhibitory concentrations (MIC) of drug candidates and antibiotics against aerobic bacteria and yeasts. Minimal bactericidal and fungicidal concentrations (MBC and MFC, respectively) were also determined in connection with the MIC determinations. The results obtained were compared with those obtained using classical agar diffusion methodology. In the MIC method, deep-well micro-titration plates are used, covered by silicone sealing mats that allow diffusion of oxygen to the wells. The appropriate broth is pipetted into the wells, followed by a standardized microbial suspension (except for sterile controls) and a dilution series of the test substance or control antibiotic or a mere control solvent. The use of white non-transparent polypropylene plates allows easy visual inspection of microbial growth. For the MBC and MFC methods, samples are taken from all wells that contain a test substance or control antibiotic and do not display growth in the MIC test. The samples are streaked on agar plates, the liquid is allowed to absorb into the agar, and finally the microbes are spread all over the plate with a bent rod. Colony counts are compared with that of the untreated microbial suspension at the beginning of the MIC test. The MIC method is suitable for high-throughput screening. 相似文献
103.
Sirpa Salo Carolina Bitu Kalle Merkku Pia Nyberg Ibrahim O. Bello Jussi Vuoristo Meeri Sutinen Hannu V?h?nikkil? Daniela E. Costea Joonas Kauppila Petri Lehenkari Dan Dayan Marilena Vered Juha Risteli Tuula Salo 《PloS one》2013,8(10)
Tumor microenvironment (TME) is an active player in carcinogenesis and changes in its composition modify cancer growth. Carcinoma-associated fibroblasts, bone marrow-derived multipotent mesenchymal stem cells (BMMSCs), and inflammatory cells can all affect the composition of TME leading to changes in proliferation, invasion and metastasis formation of carcinoma cells. In this study, we confirmed an interaction between BMMSCs and oral tongue squamous cell carcinoma (OTSCC) cells by analyzing the invasion progression and gene expression pattern. In a 3-dimensional myoma organotypic invasion model the presence of BMMSCs inhibited the proliferation but increased the invasion of OTSCC cells. Furthermore, the signals originating from OTSCC cells up-regulated the expression of inflammatory chemokines by BMMSCs, whereas BMMSC products induced the expression of known invasion linked molecules by carcinoma cells. Particularly, after the cell-cell interactions, the chemokine CCL5 was abundantly secreted from BMMSCs and a function blocking antibody against CCL5 inhibited BMMSC enhanced cancer invasion area. However, CCL5 blocking antibody did not inhibit the depth of invasion. Additionally, after exposure to BMMSCs, the expression of type I collagen mRNA in OTSCC cells was markedly up-regulated. Interestingly, also high expression of type I collagen N-terminal propeptide (PINP) in vivo correlated with the cancer-specific mortality of OTSCC patients, whereas there was no association between cancer tissue CCL5 levels and the clinical parameters. In conclusion, our results suggest that the interaction between BMMSC and carcinoma cells induce cytokine and matrix molecule expression, of which high level of type I collagen production correlates with the prognosis of OTSCC patients. 相似文献
104.
Tiina Kelkka Angela Pizzolla Juha Petteri Laurila Tomas Friman Renata Gustafsson Eva K?llberg Olof Olsson Tomas Leanderson Kristofer Rubin Marko Salmi Sirpa Jalkanen Rikard Holmdahl 《PloS one》2013,8(12)
The NADPH oxidase 2 (NOX2) complex is a professional producer of reactive oxygen species (ROS) and is mainly expressed in phagocytes. While the activity of the NOX2 complex is essential for immunity against pathogens and protection against autoimmunity, its role in the development of malignant tumors remains unclear. We compared wild type and Ncf1
m1J mutated mice, which lack functional NOX2 complex, in four different tumor models. Ncf1
m1J mutated mice developed significantly smaller tumors in two melanoma models in which B16 melanoma cells expressing a hematopoietic growth factor FLT3L or luciferase reporter were used. Ncf1
m1J mutated mice developed significantly fewer Lewis Lung Carcinoma (LLC) tumors, but the tumors that did develop, grew at a pace that was similar to the wild type mice. In the spontaneously arising prostate carcinoma model (TRAMP), tumor growth was not affected. The lack of ROS-mediated protection against tumor growth was associated with increased production of immunity-associated cytokines. A significant increase in Th2 associated cytokines was observed in the LLC model. Our present data show that ROS regulate rejection of the antigenic B16-luc and LLC tumors, whereas the data do not support a role for ROS in growth of intrinsically generated tumors. 相似文献
105.
106.
Katri Jalava Hanna Rintala Jukka Ollgren Leena Maunula Vicente Gomez-Alvarez Joana Revez Marja Palander Jenni Antikainen Ari Kauppinen Pia R?s?nen Sallamaari Siponen Outi Nyholm Aino Kyyhkynen Sirpa Hakkarainen Juhani Merentie Martti P?rn?nen Raisa Loginov Hodon Ryu Markku Kuusi Anja Siitonen Ilkka Miettinen Jorge W. Santo Domingo Marja-Liisa H?nninen Tarja Pitk?nen 《PloS one》2014,9(8)
Failures in the drinking water distribution system cause gastrointestinal outbreaks with multiple pathogens. A water distribution pipe breakage caused a community-wide waterborne outbreak in Vuorela, Finland, July 2012. We investigated this outbreak with advanced epidemiological and microbiological methods. A total of 473/2931 inhabitants (16%) responded to a web-based questionnaire. Water and patient samples were subjected to analysis of multiple microbial targets, molecular typing and microbial community analysis. Spatial analysis on the water distribution network was done and we applied a spatial logistic regression model. The course of the illness was mild. Drinking untreated tap water from the defined outbreak area was significantly associated with illness (RR 5.6, 95% CI 1.9–16.4) increasing in a dose response manner. The closer a person lived to the water distribution breakage point, the higher the risk of becoming ill. Sapovirus, enterovirus, single Campylobacter jejuni and EHEC O157:H7 findings as well as virulence genes for EPEC, EAEC and EHEC pathogroups were detected by molecular or culture methods from the faecal samples of the patients. EPEC, EAEC and EHEC virulence genes and faecal indicator bacteria were also detected in water samples. Microbial community sequencing of contaminated tap water revealed abundance of Arcobacter species. The polyphasic approach improved the understanding of the source of the infections, and aided to define the extent and magnitude of this outbreak. 相似文献
107.
Alhoranta AM Lehtinen JK Urtti AO Butcher SJ Aseyev VO Tenhu HJ 《Biomacromolecules》2011,12(9):3213-3222
A series of amphiphilic star and linear block copolymers were synthesized using ATRP. The core consisted of either polystyrene (PS) or poly(n-butyl acrylate) (PBuA), having different glass-transition (T(g)) values. These polymers were used as macroinitiators in the polymerization of the cationic 2-(dimethylamino)ethyl methacrylate (DMAEMA). The polymers were used to study the effects of polymer architecture and flexibility on the self-assembling properties, DNA complexation, and transfection. All polymers formed core-shell micelles in aqueous solutions and condensed plasmid DNA. Linear PDMAEMA-PBuA-PDMAEMA has transfection efficiency comparable to PEI25K in ARPE19 cell line. Glassy state of the micellar core and star-shaped architecture decreased the DNA transfection compared with the rubbery and linear polymer structures. The polymers showed low cellular toxicity at low nitrogen/phosphate (n/p) ratios. 相似文献
108.
Reginald Quansah Maritta S. Jaakkola Timo T. Hugg Sirpa A M. Heikkinen Jouni J. K. Jaakkola 《PloS one》2012,7(11)
Context
Studies from different geographical regions have assessed the relations between indoor dampness and mold problems and the risk of asthma, but the evidence has been inconclusive.Objective
To assess the relations between indicators of indoor dampness and mold problems and the risk of developing new asthma, and to investigate whether such relations differ according to the type of exposure.Data sources
A systematic literature search of PubMed database from 1990 through March 2012 and the reference lists of recent reviews and of relevant articles identified in our search.Study selection
Cohort/longitudinal and incident case-control studies assessing the relation between mold/dampness and new asthma were included.Data extraction
Three authors independently evaluated eligible articles and extracted relevant information using a structured form.Synthesis
Sixteen studies were included: 11 cohort and 5 incident case-control studies. The summary effect estimates (EE) based on the highest and lowest estimates for the relation between any exposure and onset of asthma were 1.50 (95% confidence interval [CI] 1.25–1.80, random-effects model, Q-statistic 38.74 (16), P = 0.001) and 1.31 (95% CI 1.09–1.58, random-effects model, Q-statistic 40.08 (16), P = 0.000), respectively. The summary effect estimates were significantly elevated for dampness (fixed-effects model: EE 1.33, 95% CI 1.12–1.56, Q-statistic 8.22 (9), P = 0.413), visible mold (random-effects model; EE 1.29, 95% CI 1.04–1.60, 30.30 (12), P = 0.001), and mold odor (random-effects model; EE 1.73, 95% CI 1.19–2.50, Q-statistics 14.85 (8), P = 0.038), but not for water damage (fixed-effects model; EE 1.12, 95% CI 0.98–1.27). Heterogeneity was observed in the study-specific effect estimates.Conclusion
The evidence indicates that dampness and molds in the home are determinants of developing asthma. The association of the presence of visible mold and especially mold odor to the risk of asthma points towards mold-related causal agents. 相似文献109.
Anna‐Maija Hannele Syrjälä Pekka Ylöstalo Piia Ruoppi Kaija Komulainen Sirpa Hartikainen Raimo Sulkava Matti Knuuttila 《Gerodontology》2012,29(1):36-42
doi: 10.1111/j.1741‐2358.2010.00396.x Dementia and oral health among subjects aged 75 years or older Objective: To study the association between diagnosed dementia and oral health, focusing on the type of dementia, among an elderly population aged 75 years or older. Background: Elderly people with dementia are at risk from oral diseases, but to date, only a few studies have analysed the association between type of dementia and oral health, and their results are inconclusive. Materials and methods: This cross‐sectional study is based on the Geriatric multi‐disciplinary strategy (Gems) study that included 76 demented and 278 non‐demented subjects. The data were collected by means of an interview and an oral clinical examination. The type of dementia was diagnosed according to DSM‐IV criteria. Poisson’s and logistic regression models were used to determine relative risks (RR), odds ratios (OR) and 95% confidence limits (CI). Results: Our results showed that patients with Alzheimer’s disease and those with other types of dementia had an increased likelihood of having carious teeth, teeth with deep periodontal pockets, and poor oral and denture hygiene, compared with non‐demented persons. The results showed that the type of dementia does not seem to be an essential determinant of oral health. Conclusions: Among the elderly aged 75 years or older, patients with Alzheimer’s disease or other types of dementia are at increased risk of poor oral health and poor oral hygiene. 相似文献
110.
Wallenius K Lappi K Mikkonen A Wickström A Vaalama A Lehtinen T Suominen L 《Biodegradation》2012,23(1):47-55
We describe a simplified microplate most-probable-number (MPN) procedure to quantify the bacterial naphthalene degrader population
in soil samples. In this method, the sole substrate naphthalene is dosed passively via gaseous phase to liquid medium and
the detection of growth is based on the automated measurement of turbidity using an absorbance reader. The performance of
the new method was evaluated by comparison with a recently introduced method in which the substrate is dissolved in inert
silicone oil and added individually to each well, and the results are scored visually using a respiration indicator dye. Oil-contaminated
industrial soil showed slightly but significantly higher MPN estimate with our method than with the reference method. This
suggests that gaseous naphthalene was dissolved in an adequate concentration to support the growth of naphthalene degraders
without being too toxic. The dosing of substrate via gaseous phase notably reduced the work load and risk of contamination.
The result scoring by absorbance measurement was objective and more reliable than measurement with indicator dye, and it also
enabled further analysis of cultures. Several bacterial genera were identified by cloning and sequencing of 16S rRNA genes
from the MPN wells incubated in the presence of gaseous naphthalene. In addition, the applicability of the simplified MPN
method was demonstrated by a significant positive correlation between the level of oil contamination and the number of naphthalene
degraders detected in soil. 相似文献