全文获取类型
收费全文 | 369篇 |
免费 | 12篇 |
国内免费 | 2篇 |
出版年
2022年 | 3篇 |
2021年 | 4篇 |
2020年 | 2篇 |
2019年 | 7篇 |
2018年 | 8篇 |
2017年 | 7篇 |
2016年 | 9篇 |
2015年 | 9篇 |
2014年 | 14篇 |
2013年 | 41篇 |
2012年 | 18篇 |
2011年 | 21篇 |
2010年 | 10篇 |
2009年 | 10篇 |
2008年 | 34篇 |
2007年 | 35篇 |
2006年 | 16篇 |
2005年 | 25篇 |
2004年 | 23篇 |
2003年 | 16篇 |
2002年 | 14篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 6篇 |
1998年 | 7篇 |
1997年 | 7篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 4篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
排序方式: 共有383条查询结果,搜索用时 218 毫秒
21.
Konno H Hiura N Makabe H Abe M Miyoshi H 《Bioorganic & medicinal chemistry letters》2004,14(3):629-632
To elucidate the inhibitory action of acetogenins, we synthesized an acetogenin derivative which possesses tetraol in place of the tetrahydrofuran ring and examined its inhibitory activity against bovine heart mitochondrial complex I. Our results indicate that these hydroxy groups are an essential structural factor though it is not effective as bis-THF hydroxy groups combination. 相似文献
22.
The Toll-like receptor 5 stimulus bacterial flagellin induces maturation and chemokine production in human dendritic cells 总被引:25,自引:0,他引:25
Means TK Hayashi F Smith KD Aderem A Luster AD 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(10):5165-5175
Toll-like receptors (TLRs) are pattern recognition receptors that serve an important function in detecting pathogens and initiating inflammatory responses. Upon encounter with foreign Ag, dendritic cells (DCs) go through a maturation process characterized by an increase in surface expression of MHC class II and costimulatory molecules, which leads to initiation of an effective immune response in naive T cells. The innate immune response to bacterial flagellin is mediated by TLR5, which is expressed on human DCs. Therefore, we sought to investigate whether flagellin could induce DC maturation. Immature DCs were cultured in the absence or presence of flagellin and monitored for expression of cell surface maturation markers. Stimulation with flagellin induced increased surface expression of CD83, CD80, CD86, MHC class II, and the lymph node-homing chemokine receptor CCR7. Flagellin stimulated the expression of chemokines active on neutrophils (IL-8/CXC chemokine ligand (CXCL)8, GRO-alpha/CXCL1, GRO-beta/CXCL2, GRO-gamma/CXCL3), monocytes (monocyte chemoattractant protein-1/CC chemokine ligand (CCL)2), and immature DCs (macrophage-inflammatory protein-1 alpha/CCL3, macrophage-inflammatory protein-1 beta/CCL4), but not chemokines active on effector T cells (IFN-inducible protein-10 kDa/CXCL10, monokine induced by IFN-gamma/CXCL9, IFN-inducible T cell alpha chemoattractant/CXCL11). However, stimulating DCs with both flagellin and IFN-inducible protein-10 kDa, monokine induced by IFN-gamma, and IFN-inducible T cell alpha chemoattractant expression, whereas stimulation with IFN-beta or flagellin alone failed to induce these chemokines. In functional assays, flagellin-matured DCs displayed enhanced T cell stimulatory activity with a concomitant decrease in endocytic activity. Finally, DCs isolated from mouse spleens or bone marrows were shown to not express TLR5 and were not responsive to flagellin stimulation. These results demonstrate that flagellin can directly stimulate human but not murine DC maturation, providing an additional mechanism by which motile bacteria can initiate an acquired immune response. 相似文献
23.
Ap-2 and Ikaros regulate transcription of human placental leucine aminopeptidase/oxytocinase gene. 总被引:4,自引:0,他引:4
24.
25.
Increased binding and chemotactic capacities of PDGF-BB on fibroblasts in radiation pneumonitis 总被引:3,自引:0,他引:3
Tada H Ogushi F Tani K Nishioka Y Miyata JY Sato K Asano T Sone S 《Radiation research》2003,159(6):805-811
Although pulmonary fibrosis is a frequent and serious consequence of radiotherapy for thoracic malignant diseases such as lung cancer, the pathogenesis of this radiation-induced lung disorder remains unclear. To clarify the mechanisms underlying radiation pneumonitis and pulmonary fibrosis, we investigated the expression of platelet-derived growth factor receptor (PDGFR) on fibroblasts obtained from irradiated rat lungs and on control fibroblasts. Whole lungs of male Wistar rats were irradiated with a single dose of 15 Gy, and lung fibroblasts were isolated at 4 weeks after the irradiation. The chemotactic response of irradiated lung fibroblasts to PDGF-BB was significantly higher than that of control lung fibroblasts, whereas there was no significant difference between irradiated lung fibroblasts and control lung fibroblasts in the response to PDGF-AA. Receptor binding assay showed more specific binding sites for PDGF-BB on irradiated lung fibroblasts than on control lung fibroblasts, and the displacement of (125)I-labeled PDGF binding to fibroblasts by unlabeled PDGF showed that (125)I-labeled PDGF-BB was displaced by PDGF-BB but not by PDGF-AA. These results suggest that the increased binding sites for PDGF-BB on irradiated lung fibroblasts correspond mainly to PDGFRB. Scatchard analysis of the saturation data demonstrated an approximately twofold increase both in the number of PDGF-BB binding sites and in the binding affinity in irradiated lung fibroblasts compared to that in control lung fibroblasts. Those results suggest that the increased chemotactic response of irradiated lung fibroblasts to PDGF-BB is related to the overexpression of PDGFRB, which may have an important role in the pathogenesis of radiation-induced pneumonitis and pulmonary fibrosis. 相似文献
26.
Nawa A Nishimori K Lin P Maki Y Moue K Sawada H Toh Y Fumitaka K Nicolson GL 《Journal of cellular biochemistry》2000,79(2):202-212
27.
Shinji Sudoh Yuuki Kawamura Shinji Sato §Rong Wang ‡Takaomi C. Saido †Fumitaka Oyama Yoshiyuki Sakaki Hiroto Komano Katsuhiko Yanagisawa 《Journal of neurochemistry》1998,71(4):1535-1543
Abstract: Mutations in the presenilin genes PS1 and PS2 cause the most common form of early-onset familial Alzheimer's disease. The influence of PS1 mutations on the generation of endogenous intracellular amyloid β-protein (Aβ) species was assessed using a highly sensitive immunoblotting technique with inducible mouse neuro-blastoma (Neuro 2a) cell lines expressing the human wild-type (wt) or mutated PS1 (M146L or Δexon 10). The induction of mutated PS1 increased the intracellular levels of two distinct Aβ species ending at residue 42 that were likely to be Aβ1–42 and its N-terminally truncated variant(s) Aβx-42. The induction of mutated PS1 resulted in a higher level of intracellular Aβ1–42 than of intracellular Aβx-42, whereas extracellular levels of Aβ1–42 and Aβx-42 were increased proportionally. In addition, the intracellular generation of these Aβ42 species in wt and mutated PS1 -induced cells was completely blocked by brefeldin A, whereas it exhibited differential sensitivities to monensin: the increased accumulation of intracellular Aβx-42 versus inhibition of intracellular Aβ1–42 generation. These data strongly suggest that Aβx-42 is generated in a proximal Golgi, whereas Aβ1–42 is generated in a distal Golgi and/or a post-Golgi compartment. Thus, it appears that PS1 mutations enhance the degree of 42-specific γ-secretase cleavage that occurs in the normal β-amyloid precursor protein processing pathway (a) in the endoplasmic reticulum or the early Golgi apparatus prior to β-secretase cleavage or (b) in the distinct sites where Aβx-42 and Aβ1–42 are generated. 相似文献
28.
29.
Tsutom Hiura 《Trees - Structure and Function》1998,12(5):274-280
Relationships between leaf or shoot size, number, and arrangement in response to light were investigated to test the hypothesis
that these characteristics are linked. In order to test this hypothesis, the divergence in allometry and shoot dynamics in
saplings of Japanese beech (Fagus crenata) obtained from four populations and having different leaf sizes were examined in a nursery under both full sun and shade
conditions. Trees with different leaf sizes also showed large differences in canopy structure, particularly when shade-grown
saplings were compared. The final leaf mass distributions of the large-leaf populations were conical or “bottom - heavy”,
while those of the small-leaf populations were planar or “top - heavy”. The slope of the allometric relations between leaf
mass and shoot and branch mass in small-leaved populations were steeper than those in large-leaf populations. The four populations
were classified into two growth types: populations producing a few large leaf and shoot modules corresponded to “stem growth
type”, and those producing many small leaf and shoot modules corresponded to “leaf growth type”. These kinds of intra-specific
variation in architecture and growth of F. crenata trees may influence the structure and dynamics of forests in accordance with differences in competitive ability or sensitivity
to disturbances such as windstorm.
Received: 18 March 1997 / Accepted: 21 October 1997 相似文献
30.
Fujito Kageyama Yoshimasa Kobayashi Gou Murohisa Erina Shimizu Fumitaka Suzuki Masataka Kikuyama Kenichi Souda Tsunehisa Kawasaki Hirotoshi Nakamura 《Biological trace element research》1998,64(1-3):185-196
Recent reports suggest the hepatic iron concentration (HIC) may influence the activity of hepatitis and the response to interferon
(IFN) therapy in patients with chronic hepatitis C (CH-C). We have evaluated iron status in 28 patients with CH-C and determined
if pretreatment iron status can predict the response to IFN-α therapy in these patients. Increased serum iron, transferrin
saturation, and ferritin levels were observed in 3 (11%), 11 (39%), and 5 (18%) patients, respectively. Hepatic iron deposits
were histologically detected in 17 (61%) patients, and 14 of them had stainable hepatocytic iron. However, all HIC values
were within the normal range (203–1279 μg/g). Seven of 17 patients treated with IFN-α for 6 mo had normalization of serum
transaminases and disappearance of serum HCV-RNA (responders). Nonresponders had a significantly higher median HIC compared
with responders (710 vs 343 μg/g, respectively;p < 0.05). There was no significant difference in other pretreatment iron parameters, serum HCV-RNA level, or HCV-genotype between
responders and nonresponders. In conclusion, mild hepatic iron accumulation occurs in patients with CH-C. Increased hepatic
iron stores are associated with poor response to IFN therapy. Pretreatment HIC may be an additional host-specific parameter
with a predictive value for responsiveness to IFN therapy, in addition to well-known predictive viral factors. 相似文献