全文获取类型
收费全文 | 1088篇 |
免费 | 93篇 |
出版年
2021年 | 11篇 |
2020年 | 8篇 |
2019年 | 8篇 |
2018年 | 17篇 |
2017年 | 11篇 |
2016年 | 21篇 |
2015年 | 25篇 |
2014年 | 34篇 |
2013年 | 59篇 |
2012年 | 54篇 |
2011年 | 54篇 |
2010年 | 40篇 |
2009年 | 39篇 |
2008年 | 61篇 |
2007年 | 54篇 |
2006年 | 48篇 |
2005年 | 39篇 |
2004年 | 41篇 |
2003年 | 35篇 |
2002年 | 44篇 |
2001年 | 33篇 |
2000年 | 51篇 |
1999年 | 45篇 |
1998年 | 26篇 |
1997年 | 21篇 |
1996年 | 15篇 |
1995年 | 9篇 |
1994年 | 6篇 |
1993年 | 5篇 |
1992年 | 22篇 |
1991年 | 17篇 |
1990年 | 30篇 |
1989年 | 21篇 |
1988年 | 17篇 |
1987年 | 23篇 |
1986年 | 14篇 |
1985年 | 5篇 |
1984年 | 15篇 |
1983年 | 8篇 |
1982年 | 10篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 7篇 |
1975年 | 11篇 |
1974年 | 5篇 |
1973年 | 5篇 |
1971年 | 9篇 |
1969年 | 8篇 |
1967年 | 6篇 |
排序方式: 共有1181条查询结果,搜索用时 15 毫秒
111.
112.
113.
Miyuki Bohgaki Masaki Matsumoto Tatsuya Atsumi Takeshi Kondo Shinsuke Yasuda Tetsuya Horita Keiichi I. Nakayama Fumihiko Okumura Shigetsugu Hatakeyama Takao Koike 《Journal of cellular and molecular medicine》2011,15(1):141-151
Antiphospholipid syndrome (APS) is characterized by thrombosis and the presence of antiphospholipid antibodies (aPL) that directly recognizes plasma β2‐glycoprotein I (β2GPI). Tissue factor (TF), the major initiator of the extrinsic coagulation system, is induced on monocytes by aPL in vitro, explaining in part the pathophysiology in APS. We previously reported that the mitogen‐activated protein kinase (MAPK) pathway plays an important role in aPL‐induced TF expression on monocytes. In this study, we identified plasma gelsolin as a protein associated with β2GPI by using immunoaffinity chromatography and mass spectrometric analysis. An in vivo binding assay showed that endogenous β2GPI interacts with plasma gelsolin, which binds to integrin a5β1 through fibronectin. The tethering of β2GPI to monoclonal anti‐β2GPI autoantibody on the cell surface was enhanced in the presence of plasma gelsolin. Immunoblot analysis demonstrated that p38 MAPK protein was phosphorylated by monoclonal anti‐β2GPI antibody treatment, and its phosphorylation was attenuated in the presence of anti‐integrin a5β1 antibody. Furthermore, focal adhesion kinase, a downstream molecule of the fibronectin‐integrin signalling pathway, was phosphorylated by anti‐β2GPI antibody treatment. These results indicate that molecules including gelsolin and integrin are involved in the anti‐β2GPI antibody‐induced MAPK pathway on monocytes and that integrin is a possible therapeutic target to modify a prothrombotic state in patients with APS. 相似文献
114.
Two novel steroidal alkaloid glycosides, lycioside A (1) and lycioside B (2) were isolated from the seeds of Lycium barbarum. Their structures were determined by various spectroscopic analyses. Compounds 1 and 2 showed inhibitory activities with the IC(50) values of 75.3 and 72.8 μM against rat intestinal sucrase, and 63.4 and 59.1 μM against rat intestinal maltase. 相似文献
115.
Satou T Matsuura M Takahashi M Murakami S Hayashi S Sadamoto K Koike K 《化学与生物多样性》2011,8(6):1132-1138
The essential oils extracted from the leaves and the shoots of five Abies species (Pinaceae) growing in Japan, i.e., A. firma, A. homolepis, A. veitchii, A. mariesii, and A. sachalinensis, were characterized by GC-FID and GC/MS analyses. The yields of the essential oils extracted from A. sachalinensis were the highest among them. A significant amount of α-pinene was contained in the essential oils of all the Abies species examined. In A. homolepis and A. veitchii, significant differences in the content of the essential oils were found depending on whether these were extracted from the leaves or from the shoots. Regarding the enantiomeric ratio of α-pinene, the (+)-enantiomer was predominant in the oil extracted from the leaves of A. firma, while (-)-α-pinene was present in higher amounts in the oils of A. veitchii (leaves and shoots), A. mariesii (leaves and shoots), and A. sachalinensis (shoots). The fact that there may be a quantitative and qualitative difference in the components of the essential oils extracted from the different parts of a plant was investigated by cluster analysis. 相似文献
116.
Yoshida T Kimura E Koike S Nojima J Futai E Sasagawa N Watanabe Y Ishiura S 《International journal of biological sciences》2011,7(3):301-307
Various vaccine therapies for Alzheimer's disease (AD) have been investigated. Here we report transgenic rice expressing amyloid β-peptide (Aβ). The Aβ42 gene fused with a green fluorescent protein gene was introduced into rice using the Agrobacterium method. When transgenic brown rice expressing Aβ was orally administered to mice, serum anti-Aβ antibody titers were elevated. The same results were observed when mice were fed boiled, transgenic brown rice. The results indicate that an edible vaccine against AD using rice may be feasible. A vaccine derived from rice would be far cheaper than existing medical vaccines. 相似文献
117.
118.
Polyclonal antibodies specific for the excitatory amino acid, kainic acid (KA), were raised in rabbits. The antibody recognized
KA but did not cross-react with other structurally related amino acids, including glutamate. We used this anti-KA antibody
to localize KA immunohistochemically in the KA-producing red alga Digenea simplex. KA immunoreactivity was most dense in the fine cylindrical thallus, which covers the middle to upper part of the alga. The
cortical cells, but not the inner layers of the main axis, and cells of the rhizoid were also stained with this antibody.
The presence of KA in cells that cover the surface of the alga might reflect its role in chemical defense. At the subcellular
level, KA immunoreactivity was most intense in the nucleus, pit plugs, and the electron-dense areas denoted as “granule bodies”,
which were found only in the pericentral cells of the thallus.
This research was supported by Ministry of Education, Culture, Sports, Science and Technology to R.S. (13660206). 相似文献
119.
Shimizu T Hayashi Y Yamasaki R Yamada J Zhang J Ukai K Koike M Mine K von Figura K Peters C Saftig P Fukuda T Uchiyama Y Nakanishi H 《Journal of neurochemistry》2005,94(3):680-690
Although of clinical importance, little is known about the mechanism of seizure in neuronal ceroid lipofuscinosis (NCL). In the present study, we have attempted to elucidate the mechanism underlying the seizure of cathepsin D-deficient (CD-/-) mice that show a novel type of lysosomal storage disease with a phenotype resembling late infantile NCL. In hippocampal slices prepared from CD-/- mice at post-natal day (P)24, spontaneous burst discharges were recorded from CA3 pyramidal cells. At P24, the mean amplitude of IPSPs after stimulation of the mossy fibres was significantly smaller than that of wild-type mice, which was substantiated by the decreased level of gamma-aminobutyric acid (GABA) contents in the hippocampus measured by high-performance liquid chromatography (HPLC). At this stage, activated microglia were found to accumulate in the pyramidal cell layer of the hippocampal CA3 subfield of CD-/- mice. However, there was no significant change in the numerical density of GABAergic interneurons in the CA3 subfield of CD-/- mice at P24, estimated by counting the number of glutamate decarboxylase (GAD) 67-immunoreactive somata. In the hippocampus and the cortex of CD-/- mice at P24, some GABAergic interneurons displayed extremely high somatic granular immunoreactivites for GAD67, suggesting the lysosomal accumulation of GAD67. GAD67 levels in axon terminals abutting on to perisomatic regions of hippocampal CA3 pyramidal cells was not significantly changed in CD-/- mice even at P24, whereas the total protein levels of GAD67 in both the hippocampus and the cortex of CD-/- mice after P24 were significantly decreased as a result of degradation. Furthermore, the recombinant human GAD65/67 was rapidly digested by the lysosomal fraction prepared from the whole brain of wild-type and CD-/- mice. These observations strongly suggest that the reduction of GABA contents, presumably because of lysosomal degradation of GAD67 and lysosomal accumulation of its degraded forms, are responsible for the dysfunction of GABAergic interneurons in the hippocampal CA3 subfield of CD-/- mice. 相似文献
120.
Superoxide dismutase (SOD) as a potential inhibitory mediator of inflammation via neutrophil apoptosis 总被引:1,自引:0,他引:1
Yasui K Kobayashi N Yamazaki T Agematsu K Matsuzaki S Ito S Nakata S Baba A Koike K 《Free radical research》2005,39(7):755-762
Superoxide dismutase (SOD) is supposed to be an effective agent for neutrophil-mediated inflammation in the area of critical medicine. We investigated the involvement of SOD in the regulation of neutrophil apoptosis. Exogenously added SOD effectively induced neutrophil apoptosis, and the fluorescence patterns determined using annexin-V and the 7-AAD were similar to those seen in Fas-mediated neutrophil apoptosis. Neutrophils are short-lived leukocytes that need to be removed safely by apoptosis. The clearance of apoptotic neutrophils from sites of inflammation is a crucial determinant of the resolution of inflammation. Catalase inhibited the neutrophil apoptosis and caspase-3 activation. Spontaneous apoptosis, hydrogen peroxide and anti-Fas antibody-induced apoptosis of neutrophils were accelerated in Down's syndrome patients, in whom the SOD gene is overexpressed. Hydrogen peroxide was thought to be a possible major mediator of ROS-induced neutrophil apoptosis in caspase-dependent manner. Neutrophil apoptosis represents a crucial step in the mechanism governing the resolution of inflammation and has been suggested as a possible target for the control of neutrophil-mediated tissue injury. SOD may be a potential inhibitory mediator of neutrophil-mediated inflammation. 相似文献