全文获取类型
收费全文 | 1131篇 |
免费 | 60篇 |
出版年
2022年 | 6篇 |
2021年 | 18篇 |
2020年 | 4篇 |
2019年 | 13篇 |
2018年 | 16篇 |
2017年 | 9篇 |
2016年 | 22篇 |
2015年 | 40篇 |
2014年 | 54篇 |
2013年 | 75篇 |
2012年 | 69篇 |
2011年 | 72篇 |
2010年 | 48篇 |
2009年 | 32篇 |
2008年 | 62篇 |
2007年 | 56篇 |
2006年 | 84篇 |
2005年 | 69篇 |
2004年 | 61篇 |
2003年 | 71篇 |
2002年 | 58篇 |
2001年 | 12篇 |
2000年 | 12篇 |
1999年 | 12篇 |
1998年 | 13篇 |
1997年 | 7篇 |
1996年 | 9篇 |
1995年 | 7篇 |
1994年 | 5篇 |
1993年 | 9篇 |
1992年 | 9篇 |
1991年 | 5篇 |
1990年 | 9篇 |
1989年 | 9篇 |
1988年 | 9篇 |
1987年 | 12篇 |
1986年 | 10篇 |
1985年 | 11篇 |
1984年 | 13篇 |
1983年 | 10篇 |
1982年 | 10篇 |
1981年 | 6篇 |
1980年 | 15篇 |
1979年 | 7篇 |
1978年 | 9篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1975年 | 4篇 |
1973年 | 5篇 |
1971年 | 2篇 |
排序方式: 共有1191条查询结果,搜索用时 15 毫秒
81.
82.
Yamaguchi Y Okazaki Y Seta N Satoh T Takahashi K Ikezawa Z Kuwana M 《Arthritis research & therapy》2010,12(6):R205
Introduction
Microvasculopathy is one of the characteristic features in patients with systemic sclerosis (SSc), but underlying mechanisms still remain uncertain. In this study, we evaluated the potential involvement of monocytic endothelial progenitor cells (EPCs) in pathogenic processes of SSc vasculopathy, by determining their number and contribution to blood vessel formation through angiogenesis and vasculogenesis. 相似文献83.
84.
Noda M Kariura Y Pannasch U Nishikawa K Wang L Seike T Ifuku M Kosai Y Wang B Nolte C Aoki S Kettenmann H Wada K 《Journal of neurochemistry》2007,101(2):397-410
Bradykinin (BK) has been reported to be a mediator of brain damage in acute insults. Receptors for BK have been identified on microglia, the pathologic sensors of the brain. Here, we report that BK attenuated lipopolysaccharide (LPS)-induced release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta from microglial cells, thus acting as an anti-inflammatory mediator in the brain. This effect was mimicked by raising intracellular cAMP or stimulating the prostanoid receptors EP2 and EP4, while it was abolished by a cAMP antagonist, a prostanoid receptor antagonist, or by an inhibitor of the inducible cyclooxygenase (cyclooxygenase-2). BK also enhanced formation of prostaglandin E(2) and expression of microsomal prostaglandin E synthase. Expression of BK receptors and EP2/EP4 receptors were also enhanced. Using physiological techniques, we identified functional BK receptors not only in culture, but also in microglia from acute brain slices. BK reduced LPS-induced neuronal death in neuron-microglia co-cultures. This was probably mediated via microglia as it did not affect TNF-alpha-induced neuronal death in pure neuronal cultures. Our data imply that BK has anti-inflammatory and neuroprotective effects in the central nervous system by modulating microglial function. 相似文献
85.
Takahashi Y Okamoto Y Popiel HA Fujikake N Toda T Kinjo M Nagai Y 《The Journal of biological chemistry》2007,282(33):24039-24048
Abnormal aggregation of misfolded proteins and their deposition as inclusion bodies in the brain have been implicated as a common molecular pathogenesis of neurodegenerative diseases including Alzheimer, Parkinson, and the polyglutamine (poly(Q)) diseases, which are collectively called the conformational diseases. The poly(Q) diseases, including Huntington disease and various types of spinocerebellar ataxia, are caused by abnormal expansions of the poly(Q) stretch within disease-causing proteins, which triggers the disease-causing proteins to aggregate into insoluble beta-sheet-rich amyloid fibrils. Although oligomeric structures formed in vitro are believed to be more toxic than mature amyloid fibrils in these diseases, the existence of oligomers in vivo has remained controversial. To explore oligomer formation in cells, we employed fluorescence correlation spectroscopy (FCS), which is a highly sensitive technique for investigating the dynamics of fluorescent molecules in solution. Here we demonstrate direct evidence for oligomer formation of poly(Q)-green fluorescent protein (GFP) fusion proteins expressed in cultured cells, by showing a time-dependent increase in their diffusion time and particle size by FCS. We show that the poly(Q)-binding peptide QBP1 inhibits poly(Q)-GFP oligomer formation, whereas Congo red only inhibits the growth of oligomers, but not the initial formation of the poly(Q)-GFP oligomers, suggesting that FCS is capable of identifying poly(Q) oligomer inhibitors. We therefore conclude that FCS is a useful technique to monitor the oligomerization of disease-causing proteins in cells as well as its inhibition in the conformational diseases. 相似文献
86.
87.
We designed a simple procedure based on the angular speed of the knee joint for quantitating the patellar tendon reflex. The angular speed of the knee joint is calculated from acceleration data generated in response to the tapping force applied to the patellar tendon with a customized tendon hammer and measured using a tri-axial accelerometer placed at the ankle joint. Data were collected and processed using a signal analyzer and a notebook PC. The results obtained using standard equipment were similar to those generated by more elaborate devices. For instance, the time delay (29.6+/-6.0 ms) and the acceleration time (150.8+/-19.5 ms) of the speed response were quite constant for all participants within the range of tapping forces normally applied during physical examinations. Representative relationships between the peak tapping force and the peak angular speed also closely fit with the exponential model (the average coefficient of determination, 0.70; range, 0.43-0.97). In contrast, the mean asymptotic value of the peak angular speed (Omega(pas)) was 160+/-67 degrees/s for spastic individuals, compared with only 72+/-21 degrees/s for healthy individuals. The important features of this method are portability, ease of use, and non-constraint of solicited reflex responses. 相似文献
88.
Suppression of viral replication by stress-inducible GADD34 protein via the mammalian serine/threonine protein kinase mTOR pathway 总被引:1,自引:0,他引:1
Minami K Tambe Y Watanabe R Isono T Haneda M Isobe K Kobayashi T Hino O Okabe H Chano T Inoue H 《Journal of virology》2007,81(20):11106-11115
GADD34 is a protein that is induced by a variety of stressors, including DNA damage, heat shock, nutrient deprivation, energy depletion, and endoplasmic reticulum stress. Here, we demonstrated that GADD34 induced by vesicular stomatitis virus (VSV) infection suppressed viral replication in wild-type (WT) mouse embryo fibroblasts (MEFs), whereas replication was enhanced in GADD34-deficient (GADD34-KO) MEFs. Enhanced viral replication in GADD34-KO MEFs was reduced by retroviral gene rescue of GADD34. The level of VSV protein expression in GADD34-KO MEFs was significantly higher than that in WT MEFs. Neither phosphorylation of eIF2alpha nor cellular protein synthesis was correlated with viral replication in GADD34-KO MEFs. On the other hand, phosphorylation of S6 and 4EBP1, proteins downstream of mTOR, was suppressed by VSV infection in WT MEFs but not in GADD34-KO MEFs. GADD34 was able to associate with TSC1/2 and dephosphorylate TSC2 at Thr1462. VSV replication was higher in TSC2-null cells than in TSC2-expressing cells, and constitutively active Akt enhanced VSV replication. On the other hand, rapamycin, an mTOR inhibitor, significantly suppressed VSV replication in GADD34-KO MEFs. These findings demonstrate that GADD34 induced by VSV infection suppresses viral replication via mTOR pathway inhibition, indicating that cross talk between stress-inducible GADD34 and the mTOR signaling pathway plays a critical role in antiviral defense. 相似文献
89.
Kinins have been reported to be produced and act at the site of injury and inflammation. Despite many reports that they are likely to initiate a particular cascade of inflammatory events, bradykinin (BK) has anti-inflammatory effects in the brain mediated by glial cells. In the present review, we have attempted to describe the complex responses and immediate reaction of glial cells to BK. Glial cells express BK receptors and induce Ca(2+)-dependent signal cascades. Among them, production of prostaglandin E(2) (PGE(2)), via B(1) receptors in primary cultured microglia, has a negative feedback effect on lipopolysaccharide (LPS)-induced release of tumor necrosis factor-alpha (TNF-alpha) via increasing intracellular cyclic adenosine monophosphate (cAMP). In addition, BK up-regulates the production of neurotrophic factors such as nerve growth factor (NGF) via B(2) receptors in astrocytes. These results suggest that BK may have anti-inflammatory and neuroprotective effects in the brain through multiple functions on glial cells. These observations may help to understand the paradox on the role of kinins in the central nervous system and may be useful for therapeutic strategy. 相似文献
90.
Kadomatsu T Mori M Terada K 《Biochemical and biophysical research communications》2007,361(2):516-521
The mitochondrial serine protease Omi/HtrA2 has a proapoptotic role in mammalian cells. However, neither the topology nor the processing of Omi in mitochondria is clearly understood. To determine the topology of Omi in the mitochondrial IMS, EGFP fusions were expressed with the entire N-terminal segment of full-length Omi (FL-Omi) (133-EGFP), and that without the transmembrane region (DeltaTM-EGFP) in the cells. Immunocytochemical staining and alkaline extraction experiments revealed that the TM determines the topology of Omi in the IMS and anchors the pro form into the inner membrane. As a result, the protease and the PDZ domains are exposed to the IMS. Mature Omi largely exists in the IMS as a soluble form. The processing sites of the precursor protein were examined by in vitro import experiments. The import of the processing mutants revealed importance of Arg80, Arg91, and Arg93 residues for the processing of the N-terminal segment of FL-Omi. These results suggest that the N-terminal segment of FL-Omi contains multiple processing sites processed by matrix processing proteases. 相似文献