全文获取类型
收费全文 | 202篇 |
免费 | 19篇 |
出版年
2019年 | 2篇 |
2017年 | 3篇 |
2016年 | 3篇 |
2015年 | 7篇 |
2014年 | 5篇 |
2013年 | 3篇 |
2012年 | 13篇 |
2011年 | 11篇 |
2010年 | 8篇 |
2009年 | 5篇 |
2008年 | 8篇 |
2007年 | 9篇 |
2006年 | 14篇 |
2005年 | 10篇 |
2004年 | 10篇 |
2003年 | 3篇 |
2002年 | 3篇 |
2001年 | 2篇 |
2000年 | 4篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1995年 | 3篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 9篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1977年 | 6篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1970年 | 5篇 |
1969年 | 3篇 |
1968年 | 2篇 |
1967年 | 2篇 |
1965年 | 2篇 |
1962年 | 1篇 |
排序方式: 共有221条查询结果,搜索用时 15 毫秒
71.
72.
73.
Daichi Maeda Yoshiyuki Akiyama Teppei Morikawa Akiko Kunita Yasunori Ota Hiroto Katoh Aya Niimi Akira Nomiya Shumpei Ishikawa Akiteru Goto Yasuhiko Igawa Masashi Fukayama Yukio Homma 《PloS one》2015,10(11)
Interstitial cystitis (IC) is a chronic bladder disease with urinary frequency, bladder discomfort or bladder pain of unknown etiology. Based on cystoscopic findings, patients with IC are classified as either Hunner-type/classic IC (HIC), presenting with a specific Hunner lesion, or non-Hunner-type IC (NHIC), presenting with no Hunner lesion, but post-hydrodistension mucosal bleeding. Inflammatory cell infiltration, composed predominantly of lymphocytes, plasma cells and epithelial denudation, has in the past been documented as a major pathological IC finding. However, the significance of the pathological evaluation of IC, especially with regard to the difference between HIC and NHIC, has been downplayed in recent years. In this study, we performed immunohistochemical quantification of infiltrating T-lymphocytes, B-lymphocytes and plasma cells, and measured the amount of residual epithelium in urinary bladder biopsy specimens taken from patients with HIC and NHIC, and those with no IC, using image analysis software. In addition, in situ hybridization of the light chains was performed to examine clonal B-cell expansion. Lymphoplasmacytic infiltration was significantly more severe in HIC specimens than in NHIC specimens (P <0.0001). Substantial lymphoplasmacytic inflammation (≥200 cells/mm2) was observed in 93% of HIC specimens, whereas only 8% of NHIC specimens were inflamed. Plasmacytic infiltration was more prominent in HIC specimens compared with NHIC and non-IC cystitis specimens (P <0.005). Furthermore, expansion of light-chain-restricted B-cells was observed in 31% of cases of HIC. The amount of residual epithelium was decreased in HIC specimens compared with NHIC specimens and non-IC cystitis specimens (P <0.0001). These results suggest that NHIC and HIC are distinct pathological entities, with the latter characterized by pancystitis, frequent clonal B-cell expansion and epithelial denudation. An abnormality in the B-cell population may be involved in the pathogenesis of HIC. 相似文献
74.
Background
Chronic obstructive pulmonary disease and emphysema develops in 15% of ex-smokers despite sustained quitting, while 10% are free of emphysema or severe lung obstruction. The cause of the incapacity of the immune system to clear the inflammation in the first group remains unclear.Methods and Findings
We searched genes that were protecting ex-smokers without emphysema, using microarrays on portions of human lungs surgically removed; we found that loss of lung function in patients with chronic obstructive pulmonary disease and emphysema was associated with a lower expression of CD46 and verified this finding by qRT-PCR and flow cytometry. Also, there was a significant association among decreased CD46+ cells with decreased CD4+T cells, apoptosis mediator CD95 and increased CD8+T cells that were protecting patients without emphysema or severe chronic obstructive pulmonary disease. CD46 not only regulates the production of T regulatory cells, which suppresses CD8+T cell proliferation, but also the complement cascade by degradation of C3b. These results were replicated in the murine smoking model, which showed increased C5a (produced by C3b) that suppressed IL12 mediated bias to T helper 1 cells and elastin co-precipitation with C3b, suggesting that elastin could be presented as an antigen. Thus, using ELISA from elastin peptides, we verified that 43% of the patients with severe early onset of chronic obstructive pulmonary disease tested positive for IgG to elastin in their serum compared to healthy controls.Conclusions
These data suggest that higher expression of CD46 in the lungs of ex-smoker protects them from emphysema and chronic obstructive pulmonary disease by clearing the inflammation impeding the proliferation of CD8+ T cells and necrosis, achieved by production of T regulatory cells and degradation of C3b; restraining the complement cascade favors apoptosis over necrosis, protecting them from autoimmunity and chronic inflammation. 相似文献75.
Kumiko Nakai Takayuki Kawato Toyoko Morita Toshimitsu Iinuma Noriaki Kamio Ning Zhao Masao Maeno 《Biochimie》2013
Angiotensin II (Ang II) plays an important role in the maintenance of bone mass and integrity by activation of the mitogen-activated protein kinases (MAPKs) and by modulation of balance between resorption by osteoclasts and formation by osteoblasts. However, the role of Ang II in the turnover of extracellular matrix (ECM) in osteoid by osteoblasts remains unclear. Therefore, we examined the effect of Ang II on the expression of matrix metalloproteinases (MMPs), plasminogen activators (PAs), and their inhibitors [i.e., tissue inhibitors of metalloproteinases (TIMPs) and PA inhibitor-1 (PAI-1)] using osteoblastic ROS17/2.8 cells. Treatment with Ang II strikingly increased the expressions of MMP-3 and -13 and promoted cell proliferation associated with reduced alkaline phosphatase activity as well as enhanced phosphorylated expression of extracellular signal-regulated kinase (ERK)1/2, p38 MAPK, and stress-activated protein kinases/c-jun N-terminal kinases (SAPK/JNK) in ROS17/2.8 cells. However, Ang II had no effect on the expression of MMP-2, -9, -14, urokinase-type PA, tissue-type PA, TIMP-1, -2, -3, and PAI-1 in cells. Losartan (AT1 receptor blocker) blocked Ang II-induced expression of MMP-3 and -13, whereas PD123319 (AT2 receptor blocker) did not completely block these responses. Losartan also blocked the Ang II-induced phosphorylation of ERK1/2, p38 MAPK, and SAPK/JNK. MAPK kinase 1/2 inhibitor PD98059 and JNK inhibitor SP600125 suppressed Ang II-induced expression of MMP-3 and -13. These results suggested that Ang II stimulated the degradation process that occurs during ECM turnover in osteoid by increasing the production of MMP-3 and -13 through MAPK signaling pathways via the AT1 receptor in osteoblasts. Furthermore, our findings suggest that Ang II does not influence the plasminogen/plasmin pathway in osteoblasts. 相似文献
76.
CD8+ T Cells are required for inflammation and destruction in cigarette smoke-induced emphysema in mice 总被引:2,自引:0,他引:2
Maeno T Houghton AM Quintero PA Grumelli S Owen CA Shapiro SD 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(12):8090-8096
Increased numbers of T lymphocytes are observed in the lungs of patients with chronic obstructive pulmonary disease, but their role in the disease process is not known. We investigated the role of CD8+ T cells in inflammatory cell recruitment and lung destruction in a cigarette smoke-induced murine model of emphysema. In contrast to wild-type C57BL/6J mice that displayed macrophage, lymphocyte, and neutrophil recruitment to the lung followed by emphysema in response to cigarette smoke, CD8+ T cell-deficient (CD8-/-) mice had a blunted inflammatory response and did not develop emphysema when exposed to long-term cigarette smoke. Further studies supported a pathogenetic pathway whereby the CD8+ T cell product, IFN-gamma-inducible protein-10, induces production of macrophage elastase (matrix metalloproteinase 12) that degrades elastin, both causing lung destruction directly and generating elastin fragments that serve as monocyte chemokines augmenting macrophage-mediated lung destruction. These studies demonstrate a requirement for CD8+ T cells for the development of cigarette smoke-induced emphysema and they provide a unifying pathway whereby CD8+ T cells are a central regulator of the inflammatory network in chronic obstructive pulmonary disease. 相似文献
77.
Characterizing phase‐related differences in behaviour of Schistocerca gregaria with spatial distribution analysis 下载免费PDF全文
Sory Cisse Saïd Ghaout Ahmed Mazih Hélène Jourdan‐Pineau Koutaro Ould Maeno Cyril Piou 《Entomologia Experimentalis et Applicata》2015,156(2):128-135
The behaviour of locusts has been studied extensively using two approaches: (1) analysing a single individual's response to a group stimulus or (2) using group conditions to look at aggregation patterns. The second approach has, in contrast with the first one, not been improved in terms of statistical analyses since the 1960s. In the present study, we propose a spatial statistics approach of point‐pattern analysis to improve the group‐based assessment of behavioural phase characterization. This diagnostic tool was developed and tested in the laboratory with comparative analysis of solitarious (isolation‐reared) and gregarious (crowd‐reared) desert locusts, Schistocerca gregaria (Forskål) (Orthoptera: Acrididae). The spatial distribution patterns of 10 either solitarious or gregarious third‐instar hoppers were characterized with nearest neighbour distance measurements in a circular arena. The temporal sequence of spatial disposition of locusts was recorded with a digital camera taking photographs at regular intervals. The approach of point‐pattern analysis focused on the spatial distribution of observed events and allowed us to make inferences about the underlying process that generated them. The results confirmed that our diagnostic tool could identify that crowd‐reared hoppers tended to aggregate more to conspecifics than isolation‐reared ones. We could also verify that isolation‐reared hoppers were less active than crowd‐reared ones, but this was only true at the beginning of the experiments. The spatial statistics approach proposed in the present study could help with observations of phase‐related differences in the behaviour of locusts. 相似文献
78.
Hongyan Cui Weijia Wu Keiichiro Okuhira Kun’ichi Miyazawa Takayuki Hattori Kimie Sai Mikihiko Naito Kazuhiro Suzuki Tetsuji Nishimura Yoshimitsu Sakamoto Akio Ogata Tomokazu Maeno Akiko Inomata Dai Nakae Akihiko Hirose Tomoko Nishimaki-Mogami 《Biochemical and biophysical research communications》2014
Because multi-wall carbon nanotubes (MWCNTs) have asbestos-like shape and size, concerns about their pathogenicity have been raised. Contaminated metals of MWCNTs may also be responsible for their toxicity. In this study, we employed high-temperature calcined fullerene nanowhiskers (HTCFNWs), which are needle-like nanofibers composed of amorphous carbon having similar sizes to MWCNTs but neither metal impurities nor tubular structures, and investigated their ability to induce production a major proinflammatory cytokine IL-1β via the Nod-like receptor pyrin domain containing 3 (NLRP3)-containing flammasome-mediated mechanism. When exposed to THP-1 macrophages, long-HTCFNW exhibited robust IL-1β production as long and needle-like MWCNTs did, but short-HTCFNW caused very small effect. IL-1β release induced by long-HTCFNW as well as by long, needle-like MWCNTs was abolished by a caspase-1 inhibitor or siRNA-knockdown of NLRP3, indicating that NLRP3-inflammasome-mediated IL-1β production by these carbon nanofibers. Our findings indicate that the needle-like shape and length, but neither metal impurities nor tubular structures of MWCNTs were critical to robust NLRP3 activation. 相似文献
79.
Hussein M. Abkallo Weimin Liu Sarina Hokama Pedro E. Ferreira Shusuke Nakazawa Yoshimasa Maeno Nguyen T. Quang Nobuyuki Kobayashi Osamu Kaneko Michael A. Huffman Satoru Kawai Ron P. Marchand Richard Carter Beatrice H. Hahn Richard Culleton 《International journal for parasitology》2014
Following the bite of an infective mosquito, malaria parasites first invade the liver where they develop and replicate for a number of days before being released into the bloodstream where they invade red blood cells and cause disease. The biology of the liver stages of malaria parasites is relatively poorly understood due to the inaccessibility of the parasites to sampling during this phase of their life cycle. Here we report the detection in blood and faecal samples of malaria parasite DNA throughout their development in the livers of mice and before the parasites begin their growth in the blood circulation. It is shown that parasite DNA derived from pre-erythrocytic stage parasites reaches the faeces via the bile. We then show that different primate malaria species can be detected by PCR in blood and faecal samples from naturally infected captive macaque monkeys. These results demonstrate that pre-erythrocytic parasites can be detected and quantified in experimentally infected animals. Furthermore, these results have important implications for both molecular epidemiology and phylogenetics of malaria parasites. In the former case, individuals who are malaria parasite negative by microscopy, but PCR positive for parasite DNA in their blood, are considered to be “sub-microscopic” blood stage parasite carriers. We now propose that PCR positivity is not necessarily an indicator of the presence of blood stage parasites, as the DNA could derive from pre-erythrocytic parasites. Similarly, in the case of molecular phylogenetics based on DNA sequences alone, we argue that DNA amplified from blood or faeces does not necessarily come from a parasite species that infects the red blood cells of that particular host. 相似文献
80.
JJ Sohn AJ Schetter HG Yfantis LA Ridnour I Horikawa MA Khan AI Robles SP Hussain A Goto ED Bowman LJ Hofseth J Bartkova J Bartek GN Wogan DA Wink CC Harris 《PloS one》2012,7(9):e44156