全文获取类型
收费全文 | 474篇 |
免费 | 38篇 |
出版年
2021年 | 3篇 |
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 7篇 |
2017年 | 6篇 |
2016年 | 12篇 |
2015年 | 9篇 |
2014年 | 13篇 |
2013年 | 20篇 |
2012年 | 22篇 |
2011年 | 25篇 |
2010年 | 12篇 |
2009年 | 10篇 |
2008年 | 19篇 |
2007年 | 26篇 |
2006年 | 22篇 |
2005年 | 17篇 |
2004年 | 18篇 |
2003年 | 32篇 |
2002年 | 30篇 |
2001年 | 16篇 |
2000年 | 14篇 |
1999年 | 12篇 |
1998年 | 11篇 |
1997年 | 16篇 |
1996年 | 11篇 |
1995年 | 11篇 |
1994年 | 9篇 |
1993年 | 3篇 |
1992年 | 9篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 6篇 |
1985年 | 2篇 |
1984年 | 7篇 |
1983年 | 6篇 |
1982年 | 11篇 |
1981年 | 8篇 |
1980年 | 5篇 |
1978年 | 5篇 |
1976年 | 4篇 |
1975年 | 3篇 |
1974年 | 3篇 |
1969年 | 3篇 |
1968年 | 1篇 |
1967年 | 4篇 |
1965年 | 1篇 |
排序方式: 共有512条查询结果,搜索用时 31 毫秒
131.
Yuichi I. Naito Noah V. Honch Yoshito Chikaraishi Naohiko Ohkouchi Minoru Yoneda 《American journal of physical anthropology》2010,143(1):31-40
Nitrogen stable isotopes analysis of individual bone collagen amino acids was applied to archeological samples as a new tool for assessing the composition of ancient human diets and calibrating radiocarbon dates. We used this technique to investigate human and faunal samples from the Kitakogane shell midden in Hokkaido, Japan (5,300–6,000 cal BP). Using compound‐specific nitrogen isotope analysis of individual amino acids, we aimed to estimate i) the quantitative contribution of marine and terrestrial protein to the human diet, and ii) the mean trophic level (TL) from which dietary protein was derived from marine ecosystems. Data were interpreted with reference to the amino acid trophic level (TLAA) model, which uses empirical amino acid δ15N from modern marine fauna to construct mathematical equations that predict the trophic position of organisms. The TLAA model produced realistic TL estimates for the Kitakogane marine animals. However, this model was not appropriate for the interpretation of human amino acid δ15N, as dietary protein is derived from both marine and terrestrial environments. Hence, we developed a series of relevant equations that considered the consumption of dietary resources from both ecosystems. Using these equations, the mean percentage of marine protein in the Kitakogane human diet was estimated to be 74%. Although this study is one of the first systematic investigations of amino acid δ15N in archeological bone collagen, we believe that this technique is extremely useful for TL reconstruction, palaeodietary interpretation, and the correction of marine reservoir effects for radiocarbon dating. Am J Phys Anthropol 143:31–40, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
132.
Luong Cong Thuc Yasushi Teshima Naohiko Takahashi Yasuko Nagano-Torigoe Kaori Ezaki Kunio Yufu Mikiko Nakagawa Masahide Hara Tetsunori Saikawa 《Apoptosis : an international journal on programmed cell death》2010,15(6):669-678
Reactive oxygen species (ROS) are important intracellular signaling molecules and are implicated in cardioprotective pathways
including ischemic preconditioning. Statins have been shown to have cardioprotective effects against ischemia/reperfusion
injury, however, the precise mechanisms remain to be elucidated. We hypothesized that ROS-mediated signaling cascade may be
involved in pravastatin-induced cardioprotection. Cultured rat cardiomyocytes were exposed to H2O2 for 30 min to induce cell injury. Pravastatin significantly suppressed H2O2-induced cell death evaluated by propidium iodide staining and the MTT assay. Incubation with pravastatin activated catalase,
and prevented a ROS burst induced by H2O2, which preserved mitochondrial membrane potential. Protective effects were induced very rapidly within 10 min, which was
concordant with the up-regulation of phosphorylated ERK1/2. L-NAME, 5HD, N-acetylcysteine (NAC) and staurosporine inhibited ERK1/2 phosphorylation and also reduced pravastatin-induced cardioprotection,
suggesting NO, mitochondrial KATP (mitoKATP) channels, ROS and PKC should be involved in the cardioprotective signaling. We also demonstrated that pravastatin moderately
up-regulated ROS generation in a 5HD-inhibitable manner. In isolated perfused rat heart experiments, pravastatin administered
10 min prior to no-flow global ischemia significantly improved left ventricular functional recovery, and also reduced infarct
size, which were attenuated by the treatment with NAC, 5HD, L-NAME or staurosporine. Administration of pravastatin from the
beginning of reperfusion also conferred cardioprotection. Pravastatin protected the cardiomyocytes against oxidative stress
by preventing the ROS burst and preserving mitochondrial function. Moderately up-regulated ROS production by mitoKATP channels opening is involved in the pro-survival signaling cascade activated by pravastatin. 相似文献
133.
Koji Isodono Tomosaburo Takahashi Hiroko Imoto Naohiko Nakanishi Takehiro Ogata Satoshi Asada Atsuo Adachi Tomomi Ueyama Hidemasa Oh Hiroaki Matsubara 《PloS one》2010,5(3)
To identify novel transmembrane and secretory molecules expressed in cardiac myocytes, signal sequence trap screening was performed in rat neonatal cardiac myocytes. One of the molecules identified was a transmembrane protein, prostatic androgen repressed message-1 (PARM-1). While PARM-1 has been identified as a gene induced in prostate in response to castration, its function is largely unknown. Our expression analysis revealed that PARM-1 was specifically expressed in hearts and skeletal muscles, and in the heart, cardiac myocytes, but not non-myocytes expressed PARM-1. Immunofluorescent staining showed that PARM-1 was predominantly localized in endoplasmic reticulum (ER). In Dahl salt-sensitive rats, high-salt diet resulted in hypertension, cardiac hypertrophy and subsequent heart failure, and significantly stimulated PARM-1 expression in the hearts, with a concomitant increase in ER stress markers such as GRP78 and CHOP. In cultured cardiac myocytes, PARM-1 expression was stimulated by proinflammatory cytokines, but not by hypertrophic stimuli. A marked increase in PARM-1 expression was observed in response to ER stress inducers such as thapsigargin and tunicamycin, which also induced apoptotic cell death. Silencing PARM-1 expression by siRNAs enhanced apoptotic response in cardiac myocytes to ER stresses. PARM-1 silencing also repressed expression of PERK and ATF6, and augmented expression of CHOP without affecting IRE-1 expression and JNK and Caspase-12 activation. Thus, PARM-1 expression is induced by ER stress, which plays a protective role in cardiac myocytes through regulating PERK, ATF6 and CHOP expression. These results suggested that PARM-1 is a novel ER transmembrane molecule involved in cardiac remodeling in hypertensive heart disease. 相似文献
134.
Tsuneo Ogawa Yurika Kawano Takuroh Imamura Kumiko Kawakita Mina Sagara Takeshi Matsuo Yousuke Kakitsubata Tadashi Ishikawa Kazuo Kitamura Kinta Hatakeyama Yujiro Asada Tatsuhiko Kodama 《Obesity (Silver Spring, Md.)》2010,18(9):1871-1874
Pentraxin 3 (PTX3) is an acute‐phase protein that shares structural homology with C‐reactive protein (CRP). PTX3 is produced in macrophages, endothelial cells, and adipocytes in response to inflammatory stimuli, whereas hepatocytes are the main source of CRP. Because obesity and metabolic syndrome (MetS) are considered chronic inflammatory states, PTX3 might be involved in the pathogenesis of obesity and MetS as well as CRP. Levels of CRP correlated positively with body weight, BMI, waist circumference (WC), fasting plasma glucose and interleukin (IL)‐6, and negatively with high‐density lipoprotein cholesterol and adiponectin in healthy males. In contrast, PTX3 correlated positively with adiponectin, and negatively with body weight, BMI, WC, and triglyceride. Plasma CRP significantly increased, whereas plasma PTX3 significantly decreased with increasing BMI. Plasma CRP and PTX3 levels were significantly higher and lower, respectively, in individuals who had more than one MetS component compared with those who had none. In conclusion, PTX3 and CRP antagonistically participate in the development of obesity or MetS. 相似文献
135.
136.
DNA variations in two PgiC loci were investigated in 15 strains of Arabidopsis halleri ssp. gemmifera. In a 5.5-kb region of the PgiC1 locus, 127 nucleotide substitutions and 33 length variations were observed. In a 6.0-kb region of the PgiC2 locus, 138 nucleotide substitutions and 33 length variations were observed. Frame shift, novel stop codons, and large length variations were observed in the PgiC2 coding region. These findings suggested that PgiC2 may be a pseudogene. The nucleotide diversities (pi) for the entire regions of both PgiC loci were approximately 0.0033. Tajima's test of both PgiC loci yielded significantly negative results. In the coding regions, the high proportions of replacement substitutions caused significant deviations from neutrality in McDonald and Kreitman's test. An excess of singletons and a high proportion of replacement polymorphic sites have been observed in the Adh and ChiA regions of A. halleri ssp. gemmifera. Thus, the A. halleri ssp. gemmifera population may not have reached equilibrium, and thus nonneutral patterns of DNA polymorphism were observed. 相似文献
137.
Matsuda A Itoh Y Koshikawa N Akizawa T Yana I Seiki M 《The Journal of biological chemistry》2003,278(38):36350-36357
MT6-MMP/MMP-25 is the latest member of the membrane-type matrix metalloproteinase (MT-MMP) subgroup in the MMP family and is expressed in neutrophils and some brain tumors. The proteolytic activity of MT6-MMP has been studied using recombinant catalytic fragments and shown to degrade several components of the extracellular matrix. However, the activity is possibly modulated further by the C-terminal hemopexin-like domain, because some MMPs are known to interact with other proteins through this domain. To explore the possible function of this domain, we purified a recombinant MT6-MMP with the hemopexin-like domain as a soluble form using a Madin-Darby canine kidney cell line as a producer. Mature and soluble MT6-MMP processed at the furin motif was purified as a 45-kDa protein together with a 46-kDa protein having a single cleavage in the hemopexin-like domain. Interestingly, 73- and 70-kDa proteins were co-purified with the soluble MT6-MMP by forming stable complexes. They were identified as clusterin, a major component of serum, by N-terminal amino acid sequencing. MT1-MMP that also has a hemopexin-like domain did not form a complex with clusterin. MT6-MMP forming a complex with clusterin was detected in human neutrophils as well. The enzyme activity of the soluble MT6-MMP was inactive in the clusterin complex. Purified clusterin was inhibitory against the activity of soluble MT6-MMP. On the other hand, it had no effect on the activities of MMP-2 and soluble MT1-MMP. Because clusterin is an abundant protein in the body fluid in tissues, it may act as a negative regulator of MT6-MMP in vivo. 相似文献
138.
Binding to EGF receptor of a laminin-5 EGF-like fragment liberated during MMP-dependent mammary gland involution 总被引:16,自引:0,他引:16
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Schenk S Hintermann E Bilban M Koshikawa N Hojilla C Khokha R Quaranta V 《The Journal of cell biology》2003,161(1):197-209
Extracellular matrix (ECM) fragments or cryptic sites unmasked by proteinases have been postulated to affect tissue remodeling and cancer progression. Therefore, the elucidation of their identities and functions is of great interest. Here, we show that matrix metalloproteinases (MMPs) generate a domain (DIII) from the ECM macromolecule laminin-5. Binding of a recombinant DIII fragment to epidermal growth factor receptor stimulates downstream signaling (mitogen-activated protein kinase), MMP-2 gene expression, and cell migration. Appearance of this cryptic ECM ligand in remodeling mammary gland coincides with MMP-mediated involution in wild-type mice, but not in tissue inhibitor of metalloproteinase 3 (TIMP-3)-deficient mice, supporting physiological regulation of DIII liberation. These findings indicate that ECM cues may operate via direct stimulation of receptor tyrosine kinases in tissue remodeling, and possibly cancer invasion. 相似文献
139.
Codon usage in nuclear genes of four monocot and three dicot species was analyzed to find general patterns in codon choice of plant species. Codon bias was correlated with GC content at the third codon position. GC contents were higher in monocot species than in dicot species at all codon positions. The high GC contents of monocot species might be the result of relatively strong mutational bias that occurred in the lineage of the Poaceae species. In both dicot and monocot species, the effective number of codons (ENCs) for most genes was similar to that for the expected ENCs based on the GC content at the third codon positions. G and C ending codons were detected as the "preferred" codons in monocot species, as in Drosophila. Also, many "preferred" codons are the same in dicot species. Pyrimidine (C and T) is used more frequently than purine (G and A) in four-fold degenerate codon groups. 相似文献
140.