全文获取类型
收费全文 | 276篇 |
免费 | 25篇 |
出版年
2022年 | 1篇 |
2021年 | 5篇 |
2020年 | 2篇 |
2019年 | 8篇 |
2018年 | 12篇 |
2017年 | 4篇 |
2016年 | 6篇 |
2015年 | 10篇 |
2014年 | 19篇 |
2013年 | 25篇 |
2012年 | 26篇 |
2011年 | 20篇 |
2010年 | 6篇 |
2009年 | 9篇 |
2008年 | 15篇 |
2007年 | 14篇 |
2006年 | 17篇 |
2005年 | 14篇 |
2004年 | 10篇 |
2003年 | 7篇 |
2002年 | 5篇 |
2001年 | 5篇 |
2000年 | 7篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 6篇 |
1991年 | 6篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1972年 | 1篇 |
1968年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有301条查询结果,搜索用时 421 毫秒
101.
Studies involving transgenic plants with modifications in the lignin pathway reported to date, have received a relatively
preliminary characterisation in relation to the impact on vascular integrity, biomechanical properties of tissues and carbon
allocation to phenolic pools. Therefore, in this study transgenic tobacco plants (Nicotiana tabacum cv XHFD 8) expressing various levels of a bacterial 4-hydroxycinnamoyl-CoA hydratase/lyase (HCHL) gene have been characterised
for cell wall and related morphological changes. The HCHL enzyme converts p-coumaroyl-CoA to 4-hydroxybenzaldehyde thereby rerouting the phenylpropanoid pathway. Plants expressing high levels of HCHL
activity exhibited reduced lignin deposition, impaired monolignol biosynthesis and vascular integrity. The plants also exhibited
reduction in stem toughness concomitant with a massive reduction in both the cell wall esterified and soluble phenolics. A
notable result of redirecting the carbon flux was the wall-bound accretion of vanillin and vanillic acid, probably due to
the shunt pathway. Intracellular accumulation of novel metabolites such as hydroxybenzoic and vanillic acid derivatives also
occurred in the transgenic plants. A line with intermediate levels of HCHL expression conferred correspondingly reduced lignin
deposition, toughness and phenolics. This line displayed a normal morphology but distorted vasculature. Coloration of the
xylem has been previously attributed to incorporation of alternative phenolics, whereas results from this study indicate that
the coloration is likely to be due to the association of low molecular weight phenolics. There was no evidence of increased
growth or enhanced cellulose biosynthesis as a result of HCHL expression. Hence, rerouting the phenylpropanoid biosynthetic
pathway quantitatively and qualitatively modifies cell wall-bound phenolics and vascular structure. 相似文献
102.
SGTx1, a Kv channel gating-modifier toxin, binds to the interfacial region of lipid bilayers
下载免费PDF全文
![点击此处可从《Biophysical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
SGTx1 is a gating-modifier toxin that has been shown to inhibit the voltage-gated potassium channel Kv2.1. SGTx1 is thought to bind to the S3b-S4a region of the voltage-sensor, and is believed to alter the energetics of gating. Gating-modifier toxins such as SGTx1 are of interest as they can be used to probe the structure and dynamics of their target channels. Although there are experimental data for SGTx1, its interaction with lipid bilayer membranes remains to be characterized. We performed atomistic and coarse-grained molecular dynamics simulations to study the interaction of SGTx1 with a POPC and a 3:1 POPE/POPG lipid bilayer membrane. We reveal the preferential partitioning of SGTx1 into the water/membrane interface of the bilayer. We also show that electrostatic interactions between the charged residues of SGTx1 and the lipid headgroups play an important role in stabilizing SGTx1 in a bilayer environment. 相似文献
103.
The reproductive system of hermit crabs shows species-specific morphology, which can be used in phylogenetic analysis. Here, we describe the male reproductive system of the hermit crab Dardanus insignis, including morphological and biometric analyses of the spermatophore, the gonopore, and sperm ultrastructure. The morphological analyses were based on 15 selected specimens and carried out by means of light and electron microscopy. Our results indicate a reproductive system composed of lobular testes attached to a simple straight vas deferens connected to the exterior via ventral gonopores. The gonopores are ovoid, surrounded by dense serrulate setae, and covered by a membranous operculum. The spermatophores exhibit a tripartite structure, with an elongate ovoid ampulla, a long narrow stalk, and a proximal foot. The spermatozoal ultrastructure shows three main regions: an ovoid-oblong acrosomal vesicle, a nucleus, and cytoplasm with three armlike extensions. Some of these characteristics can also be found in other species of Diogenidae within the genus Dardanus and in members of Coenobitidae, a closely related family. The available information on spermatophore and spermatozoal structure may indicate a closer similarity between the genus Dardanus and the Coenobitidae, compared with other members of Diogenidae. 相似文献
104.
Mithu Chatterjee Zara Tabi Mary Galli Simon Malcomber Amy Buck Michael Muszynski Andrea Gallavotti 《The Plant cell》2014,26(7):2962-2977
Although boron has a relatively low natural abundance, it is an essential plant micronutrient. Boron deficiencies cause major crop losses in several areas of the world, affecting reproduction and yield in diverse plant species. Despite the importance of boron in crop productivity, surprisingly little is known about its effects on developing reproductive organs. We isolated a maize (Zea mays) mutant, called rotten ear (rte), that shows distinct defects in vegetative and reproductive development, eventually causing widespread sterility in its inflorescences, the tassel and the ear. Positional cloning revealed that rte encodes a membrane-localized boron efflux transporter, co-orthologous to the Arabidopsis thaliana BOR1 protein. Depending on the availability of boron in the soil, rte plants show a wide range of phenotypic defects that can be fully rescued by supplementing the soil with exogenous boric acid, indicating that rte is crucial for boron transport into aerial tissues. rte is expressed in cells surrounding the xylem in both vegetative and reproductive tissues and is required for meristem activity and organ development. We show that low boron supply to the inflorescences results in widespread defects in cell and cell wall integrity, highlighting the structural importance of boron in the formation of fully fertile reproductive organs. 相似文献
105.
Brian J. Morrison Marcus L. Hastie Yadveer S. Grewal Zara C. Bruce Chris Schmidt Brent A. Reynolds Jeffrey J. Gorman J. Alejandro Lopez 《PloS one》2012,7(12)
Breast cancer is a heterogenous disease, composed of tumour cells with differing gene expressions and phenotypes. Very few antigens have been identified and a better understanding of tumour initiating-cells as targets for therapy is critically needed. Recently, a rare subpopulation of cells within tumours has been described with the ability to: (i) initiate and sustain tumour growth; (ii) resist traditional therapies and allow for secondary tumour dissemination; and (iii) display some of the characteristics of stem cells such as self-renewal. These cells are termed tumour-initiating cells or cancer stem cells, or alternatively, in the case of breast cancer, breast cancer stem cells. Previous studies have demonstrated that breast cancer stem cells can be enriched for in “tumoursphere” culture. Proteomics represents a novel way to investigate protein expression between cells. We hypothesise that characterisation of the proteome of the breast cancer line MCF-7 tumourspheres compared to adherent/differentiated cells identifies proteins of novel interest for further isolating or targeting breast cancer stem cells. We present evidence that: (i) the proteome of adherent cells is different to the proteome of cells grown in sphere medium from either early passage (passage 2) or late passage (passage 5) spheres; (ii) that spheres are enriched in expression of a variety of tumour-relevant proteins (including MUC1 and Galectin-3); and (iii) that targeting of one of these identified proteins (galectin-3) using an inhibitor (N-acetyllactosamine) decreases sphere formation/self-renewal of MCF-7 cancer stem cells in vitro and tumourigenicity in vivo. Hence, proteomic analysis of tumourspheres may find use in identifying novel targets for future therapy. The therapeutic targeting of breast cancer stem cells, a highly clinically relevant sub-population of tumour cells, has the potential to eliminate residual disease and may become an important component of a multi-modality treatment of cancer. 相似文献
106.
107.
Zara S Macchi V De Caro R Rapino M Cataldi A Porzionato A 《European journal of histochemistry : EJH》2012,56(1):e2
In premature babies birth an high oxygen level exposure can occur and newborn hyperoxia exposure can be associated with free radical oxygen release with impairment of myocardial function, while in adult animal models short exposure to hyperoxia seems to protect heart against ischemic injury. Thus, the mechanisms and consequences which take place after hyperoxia exposure are different and related to animals age. The aim of our work has been to analyze the role played by HIF-1α in the occurrence of the morphological modifications upon hyperoxia exposure in neonatal rat heart. Hyperoxia exposure induces connective compartment increase which seems to allow enhanced blood vessels growth. An increased hypoxia inducible factor-1α (HIF-1α) translocation and vascular endothelial growth factor (VEGF) expression has been found upon 95% oxygen exposure to induce morphological modifications. Upstream pPKC-α expression increase in newborn rats exposed to 95% oxygen can suggest PKC involvement in HIF-1α activation. Since nitric oxide synthase (NOS) are involved in heart vascular regulation, endothelial NOS (e-NOS) and inducible NOS (i-NOS) expression has been investigated: a lower eNOS and an higher iNOS expression has been found in newborn rats exposed to 95% oxygen related to the evidence that hyperoxia provokes a systemic vasoconstriction and to the iNOS pro-apoptotic action, respectively. The occurrence of apoptotic events, evaluated by TUNEL and Bax expression analyses, seems more evident in sample exposed to severe hyperoxia. All in all such results suggest that in newborn rats hyperoxia can trigger oxygen free radical mediated membrane injury through a pPKCα mediated HIF-1α signalling system, even though specificity of such response could be obtained by in vivo administration to the rats of specific inhibitors of PKCα. This intracellular signalling can switch molecular events leading to blood vessels development in parallel to pro-apoptotic events due to an immature anti-oxidant defensive system in newborn rat hearts. 相似文献
108.
Schadt EE Molony C Chudin E Hao K Yang X Lum PY Kasarskis A Zhang B Wang S Suver C Zhu J Millstein J Sieberts S Lamb J GuhaThakurta D Derry J Storey JD Avila-Campillo I Kruger MJ Johnson JM Rohl CA van Nas A Mehrabian M Drake TA Lusis AJ Smith RC Guengerich FP Strom SC Schuetz E Rushmore TH Ulrich R 《PLoS biology》2008,6(5):e107
109.
The ultrastructure of the ovary during development and yolk production is poorly known in Brachyura and Majoidea in particular. Here, we describe the histology, histochemistry and ultrastructure of the adult ovarian cycle in four Mithracidae species from three different genera: Mithrax hispidus, Mithrax tortugae, Mithraculus forceps and Omalacantha bicornuta. All species showed a similar pattern of ovarian development and vitellogenesis. Macroscopically, we detected three stages of ovarian development: rudimentary (RUD), developing (DE) and mature (MAT); however, in histological and ultrastructural analyses, we identified four stages of development. The oocytes of the RUD stage, during endogenous vitellogenesis, have basophilic cytoplasm filled with dilated rough endoplasmic reticulum. The reticulum lumen showed many granular to electron-dense materials among the different stages of development. The Golgi complexes were only observed in the RUD stage and are responsible for releasing vesicles that merge to the endogenous or immature yolk vesicles. At the early DE stage, the oolemma showed many coated and endocytic vesicles at the cortex. The endocytic vesicles merge with the endogenous yolk to form the exogenous or mature yolk vesicles, always surrounded by a membrane, characterizing exogenous vitellogenesis. The exogenous yolk vesicles comprise glycoproteins, showing only neutral polysaccharides. At the late DE stage, endocytosis still occurs, but the amount of endogenous yolk decreases while the exogenous yolk increases. The late DE stage is characterized by the beginning of chorion production among the microvilli. The MAT stage is similar to the late DE, but the endogenous yolk is restricted to a few cytoplasmic areas, the ooplasma is filled with exogenous yolk, and the oolemma has very few coated vesicles. In the MAT stage, the chorion is fully formed and shows two electron-dense layers. The ovarian development of the species studied has many similarities with the very little known Majoidea in terms of the composition, arrangement and increment of the yolk vesicles during oocyte maturation. The main differences are in the vitellogenesis process, where immature yolk formation occurs without the direct participation of the mitochondria but with the participation of the rough endoplasmic reticulum in the endogenous phase. 相似文献
110.
Bilobalide, a component of the Ginkgo biloba extract (EGb 761), protects against neuronal death in global brain ischemia and in glutamate-induced excitotoxicity. 总被引:11,自引:0,他引:11
Krish Chandrasekaran Zara Mehrabian Brigitte Spinnewyn Christos Chinopoulos Katy Drieu Gary Fiskum 《Cellular and molecular biology, including cyto-enzymology》2002,48(6):663-669
In this study, the effect of bilobalide, a purified terpene lactone component of the Ginkgo biloba extract (EGb 761), and EGb 761 against ischemic injury and against glutamate-induced excitotoxic neuronal death was compared. In the case of ischemic injury, neuronal loss and the levels of mitochondrial DNA (mtDNA)-encoded cytochrome oxidase (COX) subunit III mRNA in the hippocampal regions of gerbils was measured. A significant increase in neuronal death and a significant decrease in COX III mRNA were observed in the hippocampal CA1 neurons at 7-days of reperfusion after 5 min of transient global forebrain ischemia. Oral administration of EGb 761 at 25, 50 and 100 mg/kg/day and bilobalide at 3 and 6 mg/kg/day for 7 days before ischemia progressively protected hippocampal CA1 neurons against ischemia-induced neuronal death and reductions in COX III mRNA. In rat cerebellar neuronal cultures, addition of bilobalide or EGb 761 protected in a dose-dependent manner against glutamate-induced excitotoxic neuronal death [effective concentration (EC50) = 5 microg/ml (12 microM) forbilobalide and 100 microg/ml for EGb 761]. These results suggest thatboth EGb 761 and bilobalide protect against ischemia-induced neuronal death in vivo and glutamate-induced neuronal death in vitro by synergistic mechanisms involving anti-excitotoxicity, inhibition of free radical generation, scavenging of reactive oxygen species, and regulation of mitochondrial gene expression. 相似文献