全文获取类型
收费全文 | 694篇 |
免费 | 43篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 15篇 |
2020年 | 4篇 |
2019年 | 10篇 |
2018年 | 18篇 |
2017年 | 19篇 |
2016年 | 17篇 |
2015年 | 32篇 |
2014年 | 28篇 |
2013年 | 37篇 |
2012年 | 44篇 |
2011年 | 49篇 |
2010年 | 28篇 |
2009年 | 37篇 |
2008年 | 33篇 |
2007年 | 49篇 |
2006年 | 43篇 |
2005年 | 33篇 |
2004年 | 46篇 |
2003年 | 28篇 |
2002年 | 37篇 |
2001年 | 15篇 |
2000年 | 11篇 |
1999年 | 10篇 |
1998年 | 6篇 |
1997年 | 7篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 6篇 |
1993年 | 7篇 |
1992年 | 8篇 |
1991年 | 11篇 |
1990年 | 8篇 |
1989年 | 5篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1984年 | 4篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1966年 | 2篇 |
排序方式: 共有737条查询结果,搜索用时 31 毫秒
31.
Nagamine K Onodera S Kurihara A Yasukawa T Shiku H Asano R Kumagai I Matsue T 《Biotechnology and bioengineering》2007,96(5):1008-1013
A microbial array chip with collagen gel spots entrapping living Escherichia coli (E. coli) DH5alpha was applied for the screening of recombinant protein solubilities. The alpha-fragment of beta-galactosidase (betaGal) was fused to the target protein, namely, maltose-binding protein (MBP), to monitor the solubility of MBP. Scanning electrochemical microscopy (SECM) was used to detect the release of p-aminophenol from E. coli cells catalyzed by intracellular betaGal. Comparison of the SECM-based method with the Western blotting-based method indicated that the current response obtained using SECM increased with an increase in the betaGal activity and therefore, with the soluble fraction of MBP in the host cells. 相似文献
32.
Hasegawa A Yasukawa M Sakai I Fujita S 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(2):1125-1131
33.
Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHS-R), was isolated from the rat stomach and determined to be n-octanoylated 28-amino-acid peptide. In this study, we studied the distribution of ghrelin-producing cells (ghrelin cells) in the gastrointestinal tract of male and female rainbow trout (Oncorhynchus mykiss) by immunohistochemistry using N-terminal region-recognizing antibody and also by in situ hybridization using a trout ghrelin-specific cRNA probe. Ghrelin cells were found in the mucosal layer of the stomach but not in the myenteric plexus, and no ghrelin cells were observed in other regions of the gastrointestinal tract. Ghrelin cells could be classified into two types: closed- and opened-type cells. The density of ghrelin cells increased gradually in the direction from the cardiac to pyloric portions of the stomach in both sexes. The number of ghrelin cells per unit area seemed to be higher in females than in males. In conclusion, trout ghrelin cells exist in the stomach and are classified into two types of cells, closed- and opened-type cells. 相似文献
34.
Small proline-rich protein 1A is a gp130 pathway- and stress-inducible cardioprotective protein
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Pradervand S Yasukawa H Muller OG Kjekshus H Nakamura T St Amand TR Yajima T Matsumura K Duplain H Iwatate M Woodard S Pedrazzini T Ross J Firsov D Rossier BC Hoshijima M Chien KR 《The EMBO journal》2004,23(22):4517-4525
The interleukin-6 cytokines, acting via gp130 receptor pathways, play a pivotal role in the reduction of cardiac injury induced by mechanical stress or ischemia and in promoting subsequent adaptive remodeling of the heart. We have now identified the small proline-rich repeat proteins (SPRR) 1A and 2A as downstream targets of gp130 signaling that are strongly induced in cardiomyocytes responding to biomechanical/ischemic stress. Upregulation of SPRR1A and 2A was markedly reduced in the gp130 cardiomyocyte-restricted knockout mice. In cardiomyocytes, MEK1/2 inhibitors prevented SPRR1A upregulation by gp130 cytokines. Furthermore, binding of NF-IL6 (C/EBPbeta) and c-Jun to the SPRR1A promoter was observed after CT-1 stimulation. Histological analysis revealed that SPRR1A induction after mechanical stress of pressure overload was restricted to myocytes surrounding piecemeal necrotic lesions. A similar expression pattern was found in postinfarcted rat hearts. Both in vitro and in vivo ectopic overexpression of SPRR1A protected cardiomyocytes against ischemic injury. Thus, this study identifies SPRR1A as a novel stress-inducible downstream mediator of gp130 cytokines in cardiomyocytes and documents its cardioprotective effect against ischemic stress. 相似文献
35.
Okimoto K Kouchi M Matsumoto I Sakurai J Kobayashi T Hino O 《Current molecular medicine》2004,4(8):887-893
Hereditary cancer was first described in the rat by Eker and Mossige in 1954 in Oslo. The Eker rat model of hereditary renal carcinoma (RC) was the first example of a Mendelian dominantly inherited predisposition to a specific cancer in an experimental animal, and has been contributing to the elucidation of renal carcinogenesis. Recently, we found a second hereditary RC model in the Sprague-Dawley (SD) rat, in Japan in 2000, which was named the Nihon rat. The Nihon rat is also an example of a Mendelian dominantly inherited predisposition for development of RCs like the Eker rat, which are predominantly of the clear cell type (this type represents approximately 75 % of human RCC), and develop from earlier preneoplastic lesions than the Eker rat. We performed a genetic linkage analysis of the Nihon rat using 113 backcross animals, and found that the Nihon mutation was tightly linked to genes, which are located on the distal part of rat chromosome 10. Finally, we identified a germline mutation in the Birt-Hogg-Dubé gene (Bhd) (rat chromosome 10, human chromosome 17p11.2) caused by the insertion of a single nucleotide in the Nihon rat gene sequence, resulting in a frame shift and producing a stop codon 26 amino acids downstream. Thus, the Nihon rat will contribute to understanding the BHD gene function and renal carcinogenesis. 相似文献
36.
Metalloproteases with EGF, CUB, and thrombospondin-1 domains function in molting of Caenorhabditis elegans 总被引:1,自引:0,他引:1
Functional analysis using RNAi was performed on eleven genes for metalloproteases of the M12A family in Caenorhabditis elegans and the interference of the C17G1.6 gene (nas-37) was found to cause incomplete molting. The RNAi of the C26C6.3 gene (nas-36) also caused a similar molting defect but not so severely as that of the nas-37 gene. Both the genes encode an astacin-like metalloprotease with an epidermal growth factor (EGF)-like domain, a CUB domain, and a thrombospondin-1 domain, in this order. The promoter-driven green fluorescent protein (GFP) expression analysis suggested that they are expressed in hypodermal cells throughout the larval stages and in the vulva of adult animals. In the genetic background of rde-1(ne219), where RNAi does not work, the molting defect caused by the nas-37 interference was observed when the transgenic wild-type rde-1 gene was expressed under the control of the dpy-7 promoter, known to be active in the hypodermal cells, but not under the control of the myo-3 promoter, active in the muscular cells. Therefore these proteases are thought to be secreted by the hypodermal cells and to participate in shedding of old cuticles. 相似文献
37.
Miyashita T Kawakami A Tamai M Izumi Y Mingguo H Tanaka F Abiru S Nakashima K Iwanaga N Aratake K Kamachi M Arima K Ida H Migita K Origuchi T Tagashira S Nishikaku F Eguchi K 《Biochemical and biophysical research communications》2003,312(2):397-404
Akt is known to be activated in the rheumatoid synovial tissues. We examined here functional role of Akt during tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis in rheumatoid synovial cells. Rheumatoid synovial cells in vitro were rapidly committed to apoptosis in response to TRAIL in mitochondria-dependent manner whereas Akt and extracellular signal-regulated kinase (ERK) were also phosphorylated. TRAIL-mediated apoptosis in synovial cells was significantly increased through inactivation of Akt by LY294002, however, that process was not so changed by adding ERK inhibitor, PD98059. Platelet-derived growth factor (PDGF) clearly phosphorylated both Akt and ERK in synovial cells, and PDGF pretreatment markedly suppressed TRAIL-mediated synovial cell apoptosis. The use of not PD98059 but LY294002 abrogated PDGF-mediated inhibitory effect toward TRAIL-induced apoptosis in synovial cells. The above protective effect of Akt was confirmed by the use of short interfering RNA (siRNA)-directed inhibition of Akt. Our data suggest that Akt is an endogenous inhibitor during TRAIL-mediated synovial cell apoptotic pathway, which may explain that synovial cells in situ of the rheumatoid synovial tissues are resistant toward apoptotic cell death in spite of death receptor expression. 相似文献
38.
39.
The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy 总被引:36,自引:0,他引:36
Knöll R Hoshijima M Hoffman HM Person V Lorenzen-Schmidt I Bang ML Hayashi T Shiga N Yasukawa H Schaper W McKenna W Yokoyama M Schork NJ Omens JH McCulloch AD Kimura A Gregorio CC Poller W Schaper J Schultheiss HP Chien KR 《Cell》2002,111(7):943-955
Muscle cells respond to mechanical stretch stimuli by triggering downstream signals for myocyte growth and survival. The molecular components of the muscle stretch sensor are unknown, and their role in muscle disease is unclear. Here, we present biophysical/biochemical studies in muscle LIM protein (MLP) deficient cardiac muscle that support a selective role for this Z disc protein in mechanical stretch sensing. MLP interacts with and colocalizes with telethonin (T-cap), a titin interacting protein. Further, a human MLP mutation (W4R) associated with dilated cardiomyopathy (DCM) results in a marked defect in T-cap interaction/localization. We propose that a Z disc MLP/T-cap complex is a key component of the in vivo cardiomyocyte stretch sensor machinery, and that defects in the complex can lead to human DCM and associated heart failure. 相似文献
40.