全文获取类型
收费全文 | 656篇 |
免费 | 32篇 |
国内免费 | 4篇 |
专业分类
692篇 |
出版年
2022年 | 4篇 |
2021年 | 8篇 |
2020年 | 3篇 |
2019年 | 4篇 |
2018年 | 7篇 |
2017年 | 9篇 |
2016年 | 8篇 |
2015年 | 13篇 |
2014年 | 17篇 |
2013年 | 22篇 |
2012年 | 30篇 |
2011年 | 32篇 |
2010年 | 19篇 |
2009年 | 26篇 |
2008年 | 23篇 |
2007年 | 29篇 |
2006年 | 40篇 |
2005年 | 36篇 |
2004年 | 46篇 |
2003年 | 35篇 |
2002年 | 51篇 |
2001年 | 11篇 |
2000年 | 9篇 |
1999年 | 14篇 |
1998年 | 11篇 |
1997年 | 12篇 |
1996年 | 8篇 |
1995年 | 15篇 |
1994年 | 9篇 |
1993年 | 15篇 |
1992年 | 10篇 |
1991年 | 10篇 |
1990年 | 17篇 |
1989年 | 10篇 |
1988年 | 9篇 |
1987年 | 6篇 |
1986年 | 10篇 |
1985年 | 6篇 |
1984年 | 8篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1981年 | 6篇 |
1980年 | 5篇 |
1979年 | 10篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1974年 | 2篇 |
1967年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有692条查询结果,搜索用时 15 毫秒
101.
Xiaoyu Song Biao Zhou Lingyu Cui Di Lei Pingping Zhang Guodong Yao Mingyu Xia Toshihiko Hayashi Shunji Hattori Yuko Ushiki-Kaku Shin-ichi Tashiro Satoshi Onodera Takashi Ikejima 《Neurochemical research》2017,42(4):1073-1083
Alzheimer’s disease (AD) is a progressive, neurodegenerative disease. Accumulating evidence suggests that inflammatory response, oxidative stress and autophagy are involved in amyloid β (Aβ)-induced memory deficits. Silibinin (silybin), a flavonoid derived from the herb milk thistle, is well known for its hepatoprotective activities. In this study, we investigated the neuroprotective effect of silibinin on Aβ25-35-injected rats. Results demonstrated that silibinin significantly attenuated Aβ25-35-induced memory deficits in Morris water maze and novel object-recognition tests. Silibinin exerted anxiolytic effect in Aβ25-35-injected rats as determined in elevated plus maze test. Silibinin attenuated the inflammatory responses, increased glutathione (GSH) levels and decreased malondialdehyde (MDA) levels, and upregulated autophagy levels in the Aβ25-35-injected rats. In conclusion, silibinin is a potential candidate for AD treatment because of its anti-inflammatory, antioxidant and autophagy regulating activities. 相似文献
102.
Prolactin induces MFG-E8 production in macrophages via transcription factor C/EBPβ-dependent pathway
Aziz MM Ishihara S Rumi MA Mishima Y Oshima N Kadota C Moriyama I Li YY Rahman FB Otani A Oka A Ishimura N Kadowaki Y Amano Y Kinoshita Y 《Apoptosis : an international journal on programmed cell death》2008,13(5):609-620
The lactogenic hormone prolactin (PRL) regulates milk protein gene expression in mammary glands. To maintain homeostatic balance
in the body, milk fat globule epidermal growth factor 8 (MFG-E8) is vital for phagocytic clearance of apoptotic cells. We
investigated the effects of PRL on MFG-E8 expression in macrophages by evaluating its promoter function. Macrophages were
stimulated with PRL, and the expression of MFG-E8 was determined using real-time PCR and Western blotting. The role of MFG-E8
on phagocytosis of apoptotic cells in PRL-treated macrophages was assessed using microscopy, while the response of PRL to
MFG-E8 expression was evaluated using luciferase assay. Following treatment with PRL, significant up-regulations of the PRL
receptor and MFG-E8 were observed in macrophages, though PRL-treated macrophages more efficiently engulfed apoptotic cells.
The results of MFG-E8 promoter analysis showed considerable up-regulation of promoter activity in macrophages following PRL
treatment and results from mutation analysis of the MFG-E8 promoter suggested that the C/EBPβ binding site was responsible
for PRL-induced activation of the MFG-E8 promoter. C/EBPβ activity was found to be up-regulated in PRL-treated cells as revealed
by an electrophoretic mobility shift assay (EMSA). In conclusion, PRL is a potent inducer of MFG-E8 expression in macrophages,
while its effect is mediated by the presence of a responsive element in the MFG-E8 promoter. 相似文献
103.
Ohkura S Uenoyama Y Yamada S Homma T Takase K Inoue N Maeda K Tsukamura H 《Peptides》2009,30(1):49-56
Various studies have attempted to unravel the physiological role of metastin/kisspeptin in the control of gonadotropin-releasing hormone (GnRH) release. A number of evidences suggested that the population of metastin/kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) is involved in generating a GnRH surge to induce ovulation in rodents, and thus the target of estrogen positive feedback. Females have an obvious metastin/kisspeptin neuronal population in the AVPV, but males have only a few cell bodies in the nucleus, suggesting that the absence of the surge-generating mechanism or positive feedback action in males is due to the limited AVPV metastin/kisspeptin neuronal population. On the other hand, the arcuate nucleus (ARC) metastin/kisspeptin neuronal population is considered to be involved in the regulation of tonic GnRH release. The ARC metastin/kisspeptin neurons show no sex difference in their expression, which is suppressed by gonadal steroids in both sexes. Thus, the ARC population of metastin/kisspeptin neurons is a target of estrogen negative feedback action on tonic GnRH release. The lactating rat model provided further evidence indicating that ARC metastin/kisspeptin neurons are involved in GnRH pulse generation, because pulsatile release of luteinizing hormone (LH) is profoundly suppressed by suckling stimulus and the LH pulse suppression is well associated with the suppression of ARC metastin/kisspeptin and KiSS-1 gene expression in lactating rats. 相似文献
104.
Katoh H Fujita K Takuhara Y Ogawa A Suzuki S 《Biochemical and biophysical research communications》2011,(3):1495-520
VIGG is a putative endoplasmic reticulum (ER) resident protein induced by virus infection and ER stress, and is correlated with fruit quality in grapevine. The present study was undertaken to determine the biological function of VIGG in grapevine. Experiments using fluorescent protein-VIGG fusion protein demonstrated that VIGG is localized in ER and the ER targeting sequence is in the N-terminus. The overexpression of VIGG in Arabidopsis plant led to growth retardation. The rosette leaves of VIGG-overexpressing plants were smaller than those of the control plants and rolled at 42 days after seeding. VIGG-overexpressing plants revealed robustness to ER stress as well as the low expression of ER stress marker proteins, such as the luminal binding proteins. These characteristics of VIGG-overexpressing plants were supported by a microarray experiment that demonstrated the disruption of genes related to ER stress response and flowering, as well as cation mobility, in the plants. Finally, cation homeostasis in the plants was disturbed by the overexpression of VIGG. Taken together, these results suggest that VIGG may disturb cation homeostasis in plant, which is correlated with the robustness to ER stress and growth retardation. 相似文献
105.
Teramura N Tanaka K Iijima K Hayashida O Suzuki K Hattori S Irie S 《Journal of bacteriology》2011,193(12):3049-3056
The collagenase gene was cloned from Grimontia (Vibrio) hollisae 1706B, and its complete nucleotide sequence was determined. Nucleotide sequencing showed that the open reading frame was 2,301 bp in length and encoded an 84-kDa protein of 767 amino acid residues. The deduced amino acid sequence contains a putative signal sequence and a zinc metalloprotease consensus sequence, the HEXXH motif. G. hollisae collagenase showed 60 and 59% amino acid sequence identities to Vibrio parahaemolyticus and Vibrio alginolyticus collagenase, respectively. In contrast, this enzyme showed < 20% sequence identity with Clostridium histolyticum collagenase. When the recombinant mature collagenase, which consisted of 680 amino acids with a calculated molecular mass of 74 kDa, was produced by the Brevibacillus expression system, a major gelatinolytic protein band of ~ 60 kDa was determined by zymographic analysis. This result suggested that cloned collagenase might undergo processing after secretion. Moreover, the purified recombinant enzyme was shown to possess a specific activity of 5,314 U/mg, an ~ 4-fold greater activity than that of C. histolyticum collagenase. 相似文献
106.
Although replication-coupled chromatin assembly is known to be important for the maintenance of patterns of gene expression through sequential cell divisions, the role of replication-coupled chromatin assembly in controlling cell differentiation during animal development remains largely unexplored. Here we report that the CAF-1 protein complex, an evolutionarily conserved histone chaperone that deposits histone H3-H4 proteins onto replicating DNA, is required to generate a bilateral asymmetry in the C. elegans nervous system. A mutation in 1 of 24 C. elegans histone H3 genes specifically eliminates this aspect of neuronal asymmetry by causing a defect in the formation of a histone H3-H4 tetramer and the consequent inhibition of CAF-1-mediated nucleosome formation. Our results reveal that replication-coupled nucleosome assembly is necessary to generate a bilateral asymmetry in C. elegans neuroanatomy and suggest that left-right asymmetric epigenetic regulation can establish bilateral asymmetry in the nervous system. 相似文献
107.
Helicobacter pylori is a unique bacterial species that assimilates various steroids as membrane lipid components. Our group has recently found, however, that certain steroids may impair the viability of H. pylori. In this study, we go on to reveal that estradiol, androstenedione, and progesterone (PS) all have the potential to inhibit the growth of H. pylori. Of these three steroid hormones, progesterone demonstrated the most effective anti-H. pylori action. 17α-hydroxyprogesterone caproate (17αPSCE), a synthetic progesterone derivative, had a much stronger anti-H. pylori action than progesterone, whereas 17α-hydroxyprogesterone, a natural progesterone derivative, completely failed to inhibit the growth of the organism. Progesterone and 17αPSCE were both found to kill H. pylori through their bacteriolytic action. Among five bacterial species investigated, H. pylori was the only species susceptible to the bactericidal action of progesterone and 17αPSCE. The other four species, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epiderimidis, all resisted this action. Progesterone and free-cholesterol (FC) obstructed each other's effects against the H. pylori cell. Taken in sum, these results suggest that progesterone and FC may bind to the identical region on the H. pylori cell surface. We expect these findings to contribute to the development of a novel anti-H. pylori steroidal agent. 相似文献
108.
Murakami N Ye Y Kawanishi M Aoki S Kudo N Yoshida M Nakayama EE Shioda T Kobayashi M 《Bioorganic & medicinal chemistry letters》2002,12(20):2807-2810
Bioassay-guided separation by use of the fission yeast expressing NES of Rev, a HIV-1 viral regulatory protein, resulted in isolation of valtrate (1) as a new Rev-transport inhibitor from the nucleus to cytoplasm from Valerianae Radix. Valtrate (1) also inhibited the p-24 production of HIV-1 virus without showing any cytotoxicity against the host MT-4 cells. 相似文献
109.
Kotaro Horiguchi Masashi Higuchi Saishu Yoshida Takashi Nakakura Kozue Tateno Rumi Hasegawa Shu Takigami Shunji Ohsako Takako Kato Yukio Kato 《Cell and tissue research》2014,358(2):515-525
S100β-positive cells, which do not express the classical pituitary hormones, appear to possess multifunctional properties and are assumed to be heterogeneous in the anterior pituitary gland. The presence of several protein markers has shown that S100β-positive cells are composed of populations such as stem/progenitor cells, epithelial cells, astrocytes and dendritic cells. Recently, we succeeded in separating S100β-positive cells into round-cell (dendritic-cell-like) and process-cell types. We also found the characteristic expression of anti-inflammatory factors (interleukin-6, Il-6) and membrane receptors (integrin β-6) in the round type. Here, we further investigate the function of the subpopulation of S100β-positive cells. Since IL-6 is also a paracrine factor that regulates hormone producing-cells, we examine whether a correlation exists among extracellular acid stress, IL-6 and hormone production by using primary cultures of anterior pituitary cells. Dendritic-cell-like S100β-positive cells notably expressed Gpr68 (proton receptor) and Il-6. Furthermore, the expression of Il-6 and proopiomelanocortin (Pomc) was up-regulated by extracellular acidification. The functional role of IL-6 and GPR68 in the gene expression of Pomc during extracellular acidification was also examined. Small interfering RNA for Il-6 up-regulated Pomc expression and that for Gpr68 reversed the down-regulation of Il-6 and up-regulated Pomc expression by extracellular acidification. Thus, S100β-positive dendritic-like cells can sense an increase in extracellular protons via GPR68 and respond by the production of IL-6 in order to suppress the up-regulation of Pomc expression. 相似文献
110.
Piyada Wangroongsarb Tomoko Kohda Chutima Jittaprasartsin Karun Suthivarakom Thanitchi Kamthalang Kaoru Umeda Pathom Sawanpanyalert Shunji Kozaki Kazuyoshi Ikuta 《PloS one》2014,9(1)