全文获取类型
收费全文 | 351篇 |
免费 | 25篇 |
出版年
2021年 | 5篇 |
2019年 | 8篇 |
2018年 | 3篇 |
2017年 | 4篇 |
2016年 | 9篇 |
2015年 | 9篇 |
2014年 | 12篇 |
2013年 | 20篇 |
2012年 | 19篇 |
2011年 | 23篇 |
2010年 | 12篇 |
2009年 | 14篇 |
2008年 | 16篇 |
2007年 | 7篇 |
2006年 | 18篇 |
2005年 | 20篇 |
2004年 | 16篇 |
2003年 | 27篇 |
2002年 | 30篇 |
2001年 | 5篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1998年 | 6篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1992年 | 5篇 |
1991年 | 7篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 4篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1979年 | 3篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1969年 | 2篇 |
1968年 | 3篇 |
1966年 | 1篇 |
1964年 | 1篇 |
1963年 | 1篇 |
1935年 | 1篇 |
1931年 | 1篇 |
排序方式: 共有376条查询结果,搜索用时 41 毫秒
141.
Retroviral vectors released from mouse-derived packaging cell lines are inactivated in human sera by naturally occurring antibodies due to the recognition of Galalpha1,3Galbeta1,4GlcNAc (alphagal-epitope) decorated surface proteins. In this study, an extensive analysis of the glycosylation potential of NIH3T3-derived PA317 packaging cells using combined MALDI/TOF-MS and HPAE-PAD reveals that 34% of the N-glycan moiety represents alphagal-epitope containing structures. Stable expression of glycosyltransferases and transport signal chimeras has been demonstrated to represent an efficient tool to alter cell- and species-specific glycosylation (Grabenhorst and Conradt, 1999. J. Biol. Chem. 274, 36107-36116). In order to reduce alphagal-epitope synthesis selected chimeric glycosyltransferases were constructed by fusing Golgi-signal sequences for compartment-specific localization with the catalytic domain of alpha2,3-sialyltransferase (ST3). Stable expression of these constructs in these cells resulted in a significant reduced alphagal-epitope synthesis, and moreover, a release of retroviral vectors showing an up to 3.5-fold increase in serum stability. Thus, our results suggest that the stably transfected cells stably transfected with chimeric glycosyltransferases compete efficiently with endogenous alpha1,3-galactosyltransferase. This approach allows favored glycodesign and we anticipate the applicability of such improved retroviral vectors produced by glycosylation engineered host cells for in vivo gene therapy and, furthermore, suggest the therapeutic benefit of this technology for xenotransplantation. 相似文献
142.
He Y Vines RR Wattam AR Abramochkin GV Dickerman AW Eckart JD Sobral BW 《Bioinformatics (Oxford, England)》2005,21(1):116-121
MOTIVATION: A vast amount of information about human, animal and plant pathogens has been acquired, stored and displayed in varied formats through different resources, both electronically and otherwise. However, there is no community standard format for organizing this information or agreement on machine-readable format(s) for data exchange, thereby hampering interoperation efforts across information systems harboring such infectious disease data. RESULTS: The Pathogen Information Markup Language (PIML) is a free, open, XML-based format for representing pathogen information. XSLT-based visual presentations of valid PIML documents were developed and can be accessed through the PathInfo website or as part of the interoperable web services federation known as ToolBus/PathPort. Currently, detailed PIML documents are available for 21 pathogens deemed of high priority with regard to public health and national biological defense. A dynamic query system allows simple queries as well as comparisons among these pathogens. Continuing efforts are being taken to include other groups' supporting PIML and to develop more PIML documents. AVAILABILITY: All the PIML-related information is accessible from http://www.vbi.vt.edu/pathport/pathinfo/ 相似文献
143.
Mintern JD Maurice MM Ploegh HL Schott E 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(1):699-708
Thymic selection is controlled by the interaction between TCR and MHC/peptide. Strength and quality of the signal determine whether thymocytes are selected or deleted. The factors that contribute to this signal remain poorly defined. Here we show that fetal thymic organ cultures (FTOCs) derived from OT-I transgenic mice (the OT-I TCR is restricted by K(b)-SIINFEKL) on a K(b)D(b-/-) background support positive selection, but only when provided with soluble H-2K(b)-SIINFEKL complexes. Selection of CD8 T cells is independent of the valency of the ligand or its capability to coengage CD8 molecules. Both CD8alphaalpha and CD8alphabeta T cells are selected by H-2K(b)-SIINFEKL, but only CD8alphabeta cells are capable of releasing IFN-gamma in response to the same ligand. The alpha(4)beta(7) integrin is up-regulated on postselection thymocytes from FTOCs. After adoptive transfer, FTOC-derived OT-I CD8 T cells divide in response to the agonist peptide SIINFEKL. These results establish that CD8 T cells responsive to their nominal peptide-Ag can be generated in FTOC supplemented with soluble MHC class I molecules equipped with the same peptide. 相似文献
144.
Li KW Hornshaw MP Van Der Schors RC Watson R Tate S Casetta B Jimenez CR Gouwenberg Y Gundelfinger ED Smalla KH Smit AB 《The Journal of biological chemistry》2004,279(2):987-1002
The postsynaptic density contains multiple protein complexes that together relay the presynaptic neurotransmitter input to the activation of the postsynaptic neuron. In the present study we took two independent proteome approaches for the characterization of the protein complement of the postsynaptic density, namely 1) two-dimensional gel electrophoresis separation of proteins in conjunction with mass spectrometry to identify the tryptic peptides of the protein spots and 2) isolation of the trypsin-digested sample that was labeled with isotope-coded affinity tag, followed by liquid chromatography-tandem mass spectrometry for the partial separation and identification of the peptides, respectively. Functional grouping of the identified proteins indicates that the postsynaptic density is a structurally and functionally complex organelle that may be involved in a broad range of synaptic activities. These proteins include the receptors and ion channels for glutamate neurotransmission, proteins for maintenance and modulation of synaptic architecture, sorting and trafficking of membrane proteins, generation of anaerobic energy, scaffolding and signaling, local protein synthesis, and correct protein folding and breakdown of synaptic proteins. Together, these results imply that the postsynaptic density may have the ability to function (semi-) autonomously and may direct various cellular functions in order to integrate synaptic physiology. 相似文献
145.
Stawowy P Kallisch H Kilimnik A Margeta C Seidah NG Chrétien M Fleck E Graf K 《Biochemical and biophysical research communications》2004,321(3):531-538
The IGF-1 receptor (IGF-1R) and MT1-MMP are synthesized as larger precursor proproteins, which require endoproteolytic activation by the proprotein convertases (PCs) furin/PC5 to gain full biological activity. The aim of this study was to investigate the contribution of PCs to IGF-1R and/or MT1-MMP activation in vascular smooth muscle cells (VSMCs) as well as VSMC proliferation/migration, which are key elements in vascular remodeling. Furin and PC5 mRNAs and proteins were found in VSMCs. Inhibition of furin-like PCs with the specific pharmacological inhibitor dec-CMK inhibited IGF-1R endoproteolytic activation. Inhibition of IGF-1R maturation abrogated IGF-induced IGF-1R autophosphorylation, PI3-kinase and MAPK induction, as well as VSMC proliferation (p<0.05 vs. controls), whereas it had no effect of PDGF-stimulated signaling pathways or cell growth. Both, IGF-1 and PDGF-BB, induced MT1-MMP expression, but only IGF-1-mediated MT1-MMP induction was inhibited by dec-CMK. Induction of MMP-2 by IGF-1 was inhibited by the PI3-kinase inhibitor wortmannin, but not by the MEK-inhibitor PD98059. Dec-CMK inhibited VSMC chemotaxis comparable to the effects of the MMP-inhibitor GM6001 (both p<0.05 vs. controls), supporting that MMPs are involved. In conclusion, this study demonstrates that targeting furin-like PCs and thus inhibiting IGF-1R activation is a novel target to inhibit IGF-1-mediated signaling and cell functions, such as IGF-1-induced MT1-MMP/MMP-2 in VSMCs. 相似文献
146.
147.
148.
The morphology of the olfactory organs in two sharks, the spiny dogfish and the small-spotted catshark, was studied by light microscopy and electron microscopy (TEM and SEM). The olfactory epithelium is arranged on olfactory lamellae which are provided with secondary folds. The epithelium mainly consists of microvillous receptor cells, multiciliated supporting cells and basal cells. The find of only one type of receptor cells, the microvillous type, is discussed and the condition considered a derived (apomorphic) character. The route of the water current through the olfactory organ and the different driving forces of the ventilation process are subject to discussion. In both the pelagic dogfish and the bottom-dwelling catshark the pressure difference between the incurrent and excurrent nostrils achieved by active swimming appears to be the driving force, whereas the role of the beating of the non-sensory cilia is not evident. In the bottom-dwelling catshark the ventilation of the olfactory organ is also supported by the respiratory activity. 相似文献
149.
Nimtz M Grabenhorst E Gambert U Costa J Wray V Morr M Thiem J Conradt HS 《Glycoconjugate journal》1998,15(9):873-883
Transgalactosylation of chitobiose and chitotriose employing -galactosidase from bovine testes yielded mixtures with 1-3 linked galactose (type I) and 1-4 linked galactose (type II) in a final ratio of 1:1 for the tri- and 1:1.4 for the tetrasaccharide. After 24 h incubations of the two purified oligosaccharide mixtures with large amounts (20-fold increase compared with standard conditions) of human 1, 3/4-fucosyltransferase III (FucT III), the type I tri-/tetrasaccharides were completely converted to the Lewisa structure, whereas approximately 10% fucosylation of the type II isomers to the Lewisx oligosaccharides was observed in long-term incubations.Employing large amounts of human 1, 3-fucosyltransferase VI (FucT VI), the type I trisaccharide substrate was exclusively fucosylated at the proximal O-4 substituted N-acetylglucosamine (GlcNAc) (20%) whereas almost all of the type II isomers was converted to the corresponding Lewisx product. 45% of the type I tetrasaccharide was fucosylated at the second GlcNAc solely by FucT VI. The type II isomer was almost completely 1-3 fucosylated to yield the Lewisx derivative with traces of a structure that contained an additional fucose at the reducing GlcNAc. The results obtained in the present study employing high amounts of enzyme confirmed our previous results that FucT III acts preponderantly as a 1-4 fucosyltransferase onto GlcNAc in vitro. Human FucT VI attaches fucose exclusively in an 1-3 linkage to 4-substituted GlcNAc in vitro and does not modify any 3-substituted GlcNAc to yield Lewisa oligosaccharides. With 8-methoxycarbonyloctyl glycoside acceptors used under standard conditions, FucT III acts exclusively on the type I and FucT VI only on the type II derivative. With lacto-N-tetraose, lacto-N-fucopentraose I, or LS-tetrasaccharide as substrates, FucT III modified the 3-substituted GlcNAc and the reducing glucose; FucT VI recognized only lacto-N-neotetraose as a substrate. 相似文献
150.
Martin J. Koch Hans K. Biesalski Eckart Stofft Harald Weiser Helmut E. Gabbert Hans-P. Dienes Burkard Schulz-Dobrick Karl H. Bässler 《Cell and tissue research》1990,260(3):625-628
Summary The effect of vitamin A-deficiency on jejunal Paneth cells in rats was investigated. Crystalloid particles were observed in secretion granules of Paneth cells from 6 out of 8 rats with vitamin A-deficiency. The particles were similar to those found in Paneth cells under other experimental conditions. Using an immuno-electron-microscopic technique we demonstrated a clear lysozyme immunoreactivity of these particles. In 2 vitamin A-deficient rats tubular structures have been detected in addition to the crystalloid particles. Crystalloid particles or tubular structures were not detectable in a control group of 8 vitamin A-supplemented rats. The morphological alterations of Paneth cells may be correlated to an impaired local immunity of the intestine during vitamin A-deficiency.This work represents a portion of a doctoral thesis presented by M.J. Koch in partial fullfillment for the degree of medical doctor 相似文献