全文获取类型
收费全文 | 445篇 |
免费 | 17篇 |
国内免费 | 1篇 |
出版年
2018年 | 3篇 |
2017年 | 4篇 |
2016年 | 8篇 |
2015年 | 7篇 |
2014年 | 13篇 |
2013年 | 15篇 |
2012年 | 16篇 |
2011年 | 20篇 |
2010年 | 11篇 |
2009年 | 18篇 |
2008年 | 11篇 |
2007年 | 20篇 |
2006年 | 22篇 |
2005年 | 15篇 |
2004年 | 15篇 |
2003年 | 20篇 |
2002年 | 19篇 |
2001年 | 18篇 |
2000年 | 11篇 |
1999年 | 13篇 |
1998年 | 5篇 |
1997年 | 3篇 |
1994年 | 6篇 |
1993年 | 3篇 |
1992年 | 9篇 |
1991年 | 7篇 |
1990年 | 6篇 |
1989年 | 10篇 |
1988年 | 13篇 |
1987年 | 8篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1984年 | 5篇 |
1983年 | 7篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1978年 | 8篇 |
1977年 | 7篇 |
1976年 | 3篇 |
1974年 | 3篇 |
1973年 | 5篇 |
1971年 | 4篇 |
1969年 | 3篇 |
1961年 | 3篇 |
1958年 | 3篇 |
1953年 | 2篇 |
1951年 | 3篇 |
1948年 | 3篇 |
1940年 | 2篇 |
1935年 | 3篇 |
排序方式: 共有463条查询结果,搜索用时 15 毫秒
121.
Dennis Lazof Richard W. Linton Richard J. Volk Thomas W. Rufty 《Biology of the cell / under the auspices of the European Cell Biology Organization》1992,74(1):127-134
Current controversies in root physiology relating to the uptake and translocation of mineral nutrients are presented. The opportunities for a SIMS contribution to resolve these controversies are discussed for each of the stable isotope tracers relevant to plant nutrition. It is concluded that for all major nutrients except phosphorus there are promising stable isotope tracers. At the same time, there are challenges to overcome in each case, with respect to background levels, peak interferences and sometimes sensitivity. Techniques of tissue preparation and handling are discussed in some detail, giving attention to the special requirements of plant tissue preparation and analysis for diffusable ions. It is suggested that adapting a preparation and transfer system, designed for production of bulk frozen-hydrated cryofractured specimens, to a secondary ion mass spectrometer would permit easy, rapid preparation. Additionally, this preparation minimizes several serious technical problems inherent to other preparative methods. Difficulties in quantitation are treated briefly, outlining some difficulties specific to plant tissue analysis. Prospects for future applications in plant mineral nutrition are evaluated, taking into account current instrumental developments. 相似文献
122.
Traub LM 《Biochimica et biophysica acta》2005,1744(3):415-437
Clathrin-mediated vesicular trafficking events underpin the vectorial transfer of macromolecules between several eukaryotic membrane-bound compartments. Classical models for coat operation, focused principally on interactions between clathrin, the heterotetrameric adaptor complexes, and cargo molecules, fail to account for the full complexity of the coat assembly and sorting process. New data reveal that targeting of clathrin adaptor complexes is generally supported by phosphoinositides, that cargo recognition by heterotetrameric adaptors depends on phosphorylation-driven conformational alterations, and that dedicated clathrin-associated sorting proteins (CLASPs) exist to promote the selective trafficking of specific categories of cargo. A host of accessory factors also participate in coat polymerization events, and the independently folded appendage domains that project off the heterotetrameric adaptor core function as recruitment platforms that appear to oversee assembly operations. It is also now clear that focal polymerization of branched actin microfilaments contributes to clathrin-coated vesicle assembly and movement at both plasma membrane and Golgi sites. This improved appreciation of the complex mechanisms governing clathrin-dependent sorting events reveals several common principles of clathrin operation at the Golgi and the plasma membrane. 相似文献
123.
Mishra SK Keyel PA Edeling MA Dupin AL Owen DJ Traub LM 《The Journal of biological chemistry》2005,280(19):19270-19280
The autosomal recessive hypercholesterolemia (ARH) protein plays a critical role in regulating plasma low density lipoprotein (LDL) levels. Inherited defects in ARH lead to a hypercholesterolemia that closely phenocopies that caused by a defective LDL receptor. The elevated serum LDL-cholesterol levels typical of ARH patients and the pronounced accumulation of the LDL receptor at the cell surface of hepatocytes in ARH-null mice argue that ARH operates by promoting the internalization of the LDL receptor within clathrin-coated vesicles. ARH contains an amino-terminal phosphotyrosine-binding domain that associates physically with the LDL receptor internalization sequence and with phosphoinositides. The carboxyl-terminal half of ARH contains a clathrin-binding sequence and a separate AP-2 adaptor binding region providing a plausible mechanism for how ARH can act as an endocytic adaptor or CLASP (clathrin-associated sorting protein) to couple LDL receptors with the clathrin machinery. Because the interaction with AP-2 is highly selective for the independently folded appendage domain of the beta2 subunit, we have characterized the ARH beta2 appendage-binding sequence in detail. Unlike the known alpha appendage-binding motifs, ARH requires an extensive sequence tract to bind the beta appendage with comparably high affinity. A minimal 16-residue sequence functions autonomously and depends upon ARH residues Asp253, Phe259, Leu262, and Arg266. We suggested that biased beta subunit engagement by ARH and the only other beta2 appendage selective adaptor, beta-arrestin, promotes efficient incorporation of this mechanistically distinct subset of CLASPs into clathrin-coated buds. 相似文献
124.
Linton PJ Harbertson J Bradley LM 《Journal of immunology (Baltimore, Md. : 1950)》2000,165(10):5558-5565
Activated B cells express high levels of class II MHC and costimulatory molecules and are nearly as effective as dendritic cells in their APC ability. Yet, their importance as APC in vivo is controversial and their role, if any, in the development of CD4 memory is unknown. We compared responses of CD4 cells from normal and B cell-deficient mice to keyhole limpet hemocyanin over 6 mo and observed diminished IL-2 production by cells primed in the absence of B cells. This was due to lower frequencies of Ag-responsive cells and not to decreased levels of IL-2 secretion per cell. The absence of B cells did not affect the survival of memory CD4 cells since frequencies remained stable. Despite normal dendritic cell function, multiple immunizations of B cell-deficient mice did not restore frequencies of memory cells. However, the transfer of B cells restored memory cell development. Ag presentation was not essential since B cells activated in vitro with irrelevant Ag also restored frequencies of memory cells. The results provide unequivocal evidence that B cells play a critical role in regulating clonal expansion of CD4 cells and, as such, are requisite for the optimal priming of memory in the CD4 population. 相似文献
125.
Gruen ML Plummer MR Zhang W Posey KA Linton MF Fazio S Hasty AH 《Journal of lipid research》2005,46(9):2007-2014
Obese mice without leptin (ob/ob) or the leptin receptor (db/db) have increased plasma HDL levels and accumulate a unique lipoprotein referred to as LDL/HDL1. To determine the role of apolipoprotein A-I (apoA-I) in the formation and accumulation of LDL/HDL1, both ob/ob and db/db mice were crossed onto an apoA-I-deficient (apoA-I(-/-)) background. Even though the obese apoA-I(-/-) mice had an expected dramatic decrease in HDL levels, the LDL/HDL1 particle persisted. The cholesterol in this lipoprotein range was associated with both alpha- and beta-migrating particles, confirming the presence of small LDLs and large HDLs. Moreover, in the obese apoA-I(-/-) mice, LDL particles were smaller and HDLs were more negatively charged and enriched in apoE compared with controls. This LDL/HDL1 particle was rapidly remodeled to the size of normal HDL after injection into C57BL/6 mice, but it was not catabolized in obese apoA-I(-/-) mice even though plasma hepatic lipase (HL) activity was increased significantly. The finding of decreased hepatic scavenger receptor class B type I (SR-BI) protein levels may explain the persistence of LDL/HDL1 in obese apoA-I(-/-) mice. Our studies suggest that the maturation and removal of large HDLs depends on the integrity of a functional axis of apoA-I, HL, and SR-BI. Moreover, the presence of large HDLs without apoA-I provides evidence for an apoA-I-independent pathway of cholesterol efflux, possibly sustained by apoE. 相似文献
126.
Freeman NE Rusinol AE Linton M Hachey DL Fazio S Sinensky MS Thewke D 《Journal of lipid research》2005,46(9):1933-1943
7-Ketocholesterol (7KC) is a cytotoxic component of oxidized low density lipoproteins (OxLDLs) and induces apoptosis in macrophages by a mechanism involving the activation of cytosolic phospholipase A2 (cPLA2). In the current study, we examined the role of ACAT in 7KC-induced and OxLDL-induced apoptosis in murine macrophages. An ACAT inhibitor, Sandoz 58-035, suppressed 7KC-induced apoptosis in P388D1 cells and both 7KC-induced and OxLDL-induced apoptosis in mouse peritoneal macrophages (MPMs). Furthermore, compared with wild-type MPMs, ACAT-1-deficient MPMs demonstrated significant resistance to both 7KC-induced and OxLDL-induced apoptosis. Macrophages treated with 7KC accumulated ACAT-derived [14C]cholesteryl and [3H]7-ketocholesteryl esters. Tandem LC-MS revealed that the 7KC esters contained primarily saturated and monounsaturated fatty acids. An inhibitor of cPLA2, arachidonyl trifluoromethyl ketone, prevented the accumulation of 7KC esters and inhibited 7KC-induced apoptosis in P388D1 cells. The decrease in 7KC ester accumulation produced by the inhibition of cPLA2 was reversed by supplementing with either oleic or arachidonic acid (AA); however, only AA supplementation restored the induction of apoptosis by 7KC. These results suggest that 7KC not only initiates the apoptosis pathway by activating cPLA2, as we have reported previously, but also participates in the downstream signaling pathway when esterified by ACAT to form 7KC-arachidonate. 相似文献
127.
Endocytic clathrin-coated vesicles are short-lived transport intermediates that ferry cargo macromolecules rapidly into the cell interior. Recent work from the Kirchhausen laboratory indicates that the lifetime of a coated vesicle is extremely short, and assembly of nascent coats aborts abruptly unless reinforced by additional regulatory inputs, most likely cargo capture. 相似文献
128.
Ishiguro H Yoshida H Major AS Zhu T Babaev VR Linton MF Fazio S 《The Journal of biological chemistry》2001,276(39):36742-36748
We have previously reported that the lack of apolipoprotein (apo) E expression by macrophages promotes foam cell formation in vivo. Because transgenic mice overexpressing human apoA-I from the liver (h-apoA-I TgN) are protected from the atherogenesis induced by apoE deficiency, we hypothesized that the presence of apoA-I in the vessel wall could reduce the negative effect of apoE deficiency on lesion growth. To address this issue, we used both retroviral transduction and transgenic approaches to produce in vivo systems where apoA-I is expressed from macrophages. In the retroviral transduction study, apoA-I-deficient (apoA-I(-/-)) mice reconstituted with apoE-deficient (apoE(-/-)) bone marrow cells that were infected with a retroviral vector expressing human apoA-I (MFG-HAI) had 95% lower atherosclerotic lesion area than that of recipients of apoE(-/-) bone marrow cells infected with the parental virus (MFG). To determine whether the protective effect of locally produced apoA-I was due to the lack of systemic apoA-I, we conducted a different experiment using h-apoA-I TgN mice as recipients of apoE(-/-) bone marrow with or without human apoA-I (driven by a macrophage-specific transgene defined as mphi-AI). Aortic lesion area in apoE(-/-)/mphi-AI --> h-apoA-I TgN mice was decreased by 85% compared with apoE(-/-) --> h-apoA-I TgN mice. These data demonstrate that expression of apoA-I from macrophages protects against atherogenesis without affecting plasma apoA-I and high density lipoprotein cholesterol levels. 相似文献
129.
Swift LL Farkas MH Major AS Valyi-Nagy K Linton MF Fazio S 《The Journal of biological chemistry》2001,276(25):22965-22970
We have investigated the recycling of apoE in livers of apoE(-)/- mice transplanted with wild type bone marrow (apoE(+/+) --> apoE(-)/-), a model in which circulating apoE is derived exclusively from macrophages. Nascent Golgi lipoproteins were recovered from livers of apoE(+/+) --> apoE(-)/- mice 8 weeks after transplantation. ApoE was identified with nascent d < 1.006 and with d 1.006-1.210 g/ml lipoproteins at a level approximately 6% that of nascent lipoproteins from C57BL/6 mice. Hepatocytes from apoE(+/+) --> apoE(-)/- mice were isolated and cultured in media free of exogenous apoE. ApoE was found in the media primarily on the d < 1.006 g/ml fraction, indicating a resecretion of internalized apoprotein. Secretion of apoE from C57BL/6 hepatocytes was consistent with constitutive production, whereas the majority of apoE secreted from apoE(+/+) --> apoE(-)/- hepatocytes was recovered in the last 24 h of culture. This suggests that release may be triggered by accumulation of an acceptor, such as very low density lipoproteins, in the media. In agreement with the in vivo data, total recovery of apoE from apoE(+/+) --> apoE(-)/- hepatocytes was approximately 6% that of the apoE recovered from C57BL/6 hepatocytes. Since plasma apoE levels in the transplanted mice are approximately 10% of control levels, the findings indicate that up to 60% of the internalized apoE may be reutilized under physiologic conditions. These studies provide definitive evidence for the sparing of apoE and its routing through the secretory pathway and demonstrate that internalized apoE can be resecreted in a quantitatively significant fashion. 相似文献
130.