全文获取类型
收费全文 | 322篇 |
免费 | 56篇 |
国内免费 | 1篇 |
出版年
2021年 | 3篇 |
2018年 | 2篇 |
2017年 | 3篇 |
2016年 | 3篇 |
2015年 | 8篇 |
2014年 | 10篇 |
2013年 | 10篇 |
2012年 | 17篇 |
2011年 | 10篇 |
2010年 | 15篇 |
2009年 | 9篇 |
2008年 | 11篇 |
2007年 | 7篇 |
2006年 | 13篇 |
2005年 | 13篇 |
2004年 | 12篇 |
2003年 | 10篇 |
2002年 | 11篇 |
2001年 | 12篇 |
2000年 | 13篇 |
1999年 | 14篇 |
1998年 | 11篇 |
1997年 | 11篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 7篇 |
1992年 | 15篇 |
1991年 | 13篇 |
1990年 | 10篇 |
1989年 | 15篇 |
1988年 | 14篇 |
1987年 | 11篇 |
1986年 | 6篇 |
1985年 | 8篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 3篇 |
1981年 | 5篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1967年 | 2篇 |
1963年 | 1篇 |
1959年 | 1篇 |
1954年 | 1篇 |
1950年 | 1篇 |
1933年 | 1篇 |
1924年 | 1篇 |
1923年 | 1篇 |
排序方式: 共有379条查询结果,搜索用时 203 毫秒
281.
BOBROV ALEXEY V. F. CH.; MELIKIAN ALEXANDER P.; YEMBATUROVA ELENA YU. 《Annals of botany》1999,83(6):601-618
To analyse the status and phylogeny of the genusPhyllocladus,seedsof all seven species of the genus were studied. The complexof features of thePhyllocladusreproductive system point to theisolated position of the genus within the conifers. Relationswith Podocarpaceae s. l., Taxaceae s. l. and Cephalotaxaceaeappeared to be remote because a complex of features clearlydistinguishesPhyllocladusfrom the afore-mentioned taxa. We findit advisable to circumscribe the family Phyllocladaceae as Bessey(1907) did, and place it into the order Taxales Knobl. in Warming(1890). From investigations of the seeds it appears the genusPhyllocladusconsistsof seven species, forming five groups. There is a significanttendency for transformation of the female reproductive structureswithin the generic boundaries ofPhyllocladusseeds, originallysolitary, tending to aggregate in various kinds of compact clusters.Copyright1999 Annals of Botany Company PhyllocladusL. C. & A. Rich, ex Mirb., seed anatomy, seed morphology, systematics, phylogenetic relationships, Phyllocladaceae, Podocarpaceae s. str., Acmopyleaceae, Nageiaceae, Austrotaxaceae, Amentotaxaceae, Torreyaceae, Taxaceae, s. str., Cephalotaxaceae, Taxales. 相似文献
282.
Howard CH Yim Die Wang Liang Yu Christine L White Pieter W Faber Bryan RG Williams Anthony J Sadler 《Cell research》2016,26(3):367-379
The protein kinase R (PKR) functions in the antiviral response by controlling protein translation and inflammatory cell signaling pathways. We generated a transgenic, knock-in mouse in which the endogenous PKR is expressed with a point mutation that ablates its kinase activity. This novel animal allows us to probe the kinase-dependent and -independent functions of PKR. We used this animal together with a previously generated transgenic mouse that is ablated for PKR expression to determine the role of PKR in regulating the activity of the cryopyrin inflammasome. Our data demonstrate that, in contradiction to earlier reports, PKR represses cryopyrin inflammasome activity. We demonstrate that this control is mediated through the established function of PKR to inhibit protein translation of constituents of the inflammasome to prevent initial priming during innate immune signaling. These findings identify an important role for PKR to dampen inflammation during the innate immune response and caution against the previously proposed therapeutic strategy to inhibit PKR to treat inflammation. 相似文献
283.
284.
285.
Stefan Termén E‐Jean Tan Carl‐Henrik Heldin Aristidis Moustakas 《Journal of cellular physiology》2013,228(4):801-813
Epithelial plasticity characterizes embryonic development and diseases such as cancer. Epithelial–mesenchymal transition (EMT) is a reversible and guided process of plasticity whereby embryonic or adult epithelia acquire mesenchymal properties. Multiple signaling pathways control EMT, and the transforming growth factor β (TGFβ) pathway plays a central role as its inducer. Here, we analyzed the role of the tumor suppressor protein p53 in TGFβ‐induced EMT in a well‐established mammary epithelial cell model. We found that diploid NMuMG mammary cells bi‐allelically express a wild type and a missense mutant (R277C) form of p53. Global reduction of both forms of p53 led to an enhanced EMT response to TGFβ. Conversely, stabilization of wild type p53 using the compound nutlin had a negative impact on EMT. After silencing both p53 forms, rescue experiments using either wild type or R277C mutant p53 revealed that wild type p53 inhibited, whereas the R277C mutant did not significantly affect, the TGFβ‐driven EMT response. Under serum‐free culture conditions, silencing of total p53 levels led to higher numbers of mammospheres characterized by larger size. Rescue of the silenced endogenous p53 with R277C mutant p53, in contrast, suppressed both size and numbers of the mammospheres. This work proposes that wild type p53 controls the efficiency by which mammary epithelial cells undergo EMT in response to TGFβ. J. Cell. Physiol. 228: 801–813, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
286.
Subversion of growth regulatory pathways in malignant transformation 总被引:10,自引:0,他引:10
C H Heldin C Betsholtz L Claesson-Welsh B Westermark 《Biochimica et biophysica acta》1987,907(3):219-244
287.
Geneviève Bart Nuria Ortega Vico Antti Hassinen Francois M. Pujol Ashik Jawahar Deen Aino Ruusala Raija H. Tammi Anthony Squire Paraskevi Heldin Sakari Kellokumpu Markku I. Tammi 《The Journal of biological chemistry》2015,290(18):11479-11490
In vertebrates, hyaluronan is produced in the plasma membrane from cytosolic UDP-sugar substrates by hyaluronan synthase 1–3 (HAS1–3) isoenzymes that transfer N-acetylglucosamine (GlcNAc) and glucuronic acid (GlcUA) in alternative positions in the growing polysaccharide chain during its simultaneous extrusion into the extracellular space. It has been shown that HAS2 immunoprecipitates contain functional HAS2 homomers and also heteromers with HAS3 (Karousou, E., Kamiryo, M., Skandalis, S. S., Ruusala, A., Asteriou, T., Passi, A., Yamashita, H., Hellman, U., Heldin, C. H., and Heldin, P. (2010) The activity of hyaluronan synthase 2 is regulated by dimerization and ubiquitination. J. Biol. Chem. 285, 23647–23654). Here we have systematically screened in live cells, potential interactions among the HAS isoenzymes using fluorescence resonance energy transfer (FRET) and flow cytometric quantification. We show that all HAS isoenzymes form homomeric and also heteromeric complexes with each other. The same complexes were detected both in Golgi apparatus and plasma membrane by using FRET microscopy and the acceptor photobleaching method. Proximity ligation assays with HAS antibodies confirmed the presence of HAS1-HAS2, HAS2-HAS2, and HAS2-HAS3 complexes between endogenously expressed HASs. C-terminal deletions revealed that the enzymes interact mainly via uncharacterized N-terminal 86-amino acid domain(s), but additional binding site(s) probably exist in their C-terminal parts. Of all the homomeric complexes HAS1 had the lowest and HAS3 the highest synthetic activity. Interestingly, HAS1 transfection reduced the synthesis of hyaluronan obtained by HAS2 and HAS3, suggesting functional cooperation between the isoenzymes. These data indicate a general tendency of HAS isoenzymes to form both homomeric and heteromeric complexes with potentially important functional consequences on hyaluronan synthesis. 相似文献
288.
Spyridon Konstantinidis Eva Heldin Sunil Chhatre Nigel Titchener‐Hooker 《Biotechnology progress》2012,28(5):1292-1302
High throughput approaches to facilitate the development of chromatographic separations have now been adopted widely in the biopharmaceutical industry, but issues of how to reduce the associated analytical burden remain. For example, acquiring experimental data by high level factorial designs in 96 well plates can place a considerable strain upon assay capabilities, generating a bottleneck that limits significantly the speed of process characterization. This article proposes an approach designed to counter this challenge; Strategic Assay Deployment (SAD). In SAD, a set of available analytical methods is investigated to determine which set of techniques is the most appropriate to use and how best to deploy these to reduce the consumption of analytical resources while still enabling accurate and complete process characterization. The approach is demonstrated by investigating how salt concentration and pH affect the binding of green fluorescent protein from Escherichia coli homogenate to an anion exchange resin presented in a 96‐well filter plate format. Compared with the deployment of routinely used analytical methods alone, the application of SAD reduced both the total assay time and total assay material consumption by at least 40% and 5%, respectively. SAD has significant utility in accelerating bioprocess development activities. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012 相似文献
289.
IQGAP1, an essential scaffolding protein, forms a complex with the hyaluronan receptor CD44. In this study, we have examined the importance of IQGAP1 for hyaluronan-mediated fibroblast migration and proliferation. Hyaluronan induced formation of F-actin fibers and focal adhesions, which was dependent on IQGAP1. IQGAP1 was required for hyaluronan- but not for platelet-derived growth factor (PDGF)-BB-induced cell migration, and was required for both hyaluronan- and PDGF-BB-mediated fibroblast proliferation, but not for proliferation induced by 10% fetal bovine serum. Depletion of IQGAP1 suppressed hyaluronan-induced activation of Rac1 and enhanced the activation of RhoA. Taken together, these findings indicate important roles for IQGAP1 in hyaluronan-stimulated migration and proliferation of fibroblasts. 相似文献
290.
Alvin CH Ma Rachel Lin Po-Kwok Chan Joseph CK Leung Loretta YY Chan Anming Meng Catherine M Verfaillie Raymond Liang Anskar YH Leung 《BMC developmental biology》2007,7(1):50