全文获取类型
收费全文 | 1181篇 |
免费 | 92篇 |
出版年
2023年 | 5篇 |
2022年 | 11篇 |
2021年 | 37篇 |
2020年 | 16篇 |
2019年 | 20篇 |
2018年 | 27篇 |
2017年 | 11篇 |
2016年 | 34篇 |
2015年 | 70篇 |
2014年 | 68篇 |
2013年 | 101篇 |
2012年 | 128篇 |
2011年 | 121篇 |
2010年 | 63篇 |
2009年 | 49篇 |
2008年 | 85篇 |
2007年 | 60篇 |
2006年 | 69篇 |
2005年 | 77篇 |
2004年 | 47篇 |
2003年 | 46篇 |
2002年 | 32篇 |
2001年 | 8篇 |
2000年 | 6篇 |
1999年 | 9篇 |
1998年 | 11篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 6篇 |
1991年 | 6篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1986年 | 4篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1979年 | 3篇 |
1976年 | 2篇 |
1973年 | 1篇 |
1963年 | 1篇 |
1960年 | 2篇 |
1959年 | 2篇 |
1956年 | 1篇 |
1954年 | 1篇 |
排序方式: 共有1273条查询结果,搜索用时 31 毫秒
101.
Zahra Najarzadeh Masihuz Zaman Vita Sereikaite Kristian Strmgaard Maria Andreasen Daniel E. Otzen 《The Journal of biological chemistry》2021,297(2)
Phenol-soluble modulins (PSMs), such as α-PSMs, β-PSMs, and δ-toxin, are virulence peptides secreted by different Staphylococcus aureus strains. PSMs are able to form amyloid fibrils, which may strengthen the biofilm matrix that promotes bacterial colonization of and extended growth on surfaces (e.g., cell tissue) and increases antibiotic resistance. Many components contribute to biofilm formation, including the human-produced highly sulfated glycosaminoglycan heparin. Although heparin promotes S. aureus infection, the molecular basis for this is unclear. Given that heparin is known to induce fibrillation of a wide range of proteins, we hypothesized that heparin aids bacterial colonization by promoting PSM fibrillation. Here, we address this hypothesis using a combination of thioflavin T-fluorescence kinetic studies, CD, FTIR, electron microscopy, and peptide microarrays to investigate the mechanism of aggregation, the structure of the fibrils, and identify possible binding regions. We found that heparin accelerates fibrillation of all α-PSMs (except PSMα2) and δ-toxin but inhibits β-PSM fibrillation by blocking nucleation or reducing fibrillation levels. Given that S. aureus secretes higher levels of α-PSM than β-PSM peptides, heparin is therefore likely to promote fibrillation overall. Heparin binding is driven by multiple positively charged lysine residues in α-PSMs and δ-toxins, the removal of which strongly reduced binding affinity. Binding of heparin did not affect the structure of the resulting fibrils, that is, the outcome of the aggregation process. Rather, heparin provided a scaffold to catalyze or inhibit fibrillation. Based on our findings, we speculate that heparin may strengthen the bacterial biofilm and therefore enhance colonization via increased PSM fibrillation. 相似文献
102.
Henrik Lütken James R. Lloyd Mikkel A. Glaring Lone Baunsgaard Kristian Holst Laursen Anna Haldrup Jens Kossmann Andreas Blennow 《Planta》2010,232(5):1127-1139
Two glucanotransferases, disproportionating enzyme 1 (StDPE1) and disproportionating enzyme 2 (StDPE2), were repressed using
RNA interference technology in potato, leading to plants repressed in either isoform individually, or both simultaneously.
This is the first detailed report of their combined repression. Plants lacking StDPE1 accumulated slightly more starch in
their leaves than control plants and high levels of maltotriose, while those lacking StDPE2 contained maltose and large amounts
of starch. Plants repressed in both isoforms accumulated similar amounts of starch to those lacking StDPE2. In addition, they
contained a range of malto-oligosaccharides from maltose to maltoheptaose. Plants repressed in both isoforms had chlorotic
leaves and did not grow as well as either the controls or lines where only one of the isoforms was repressed. Examination
of photosynthetic parameters suggested that this was most likely due to a decrease in carbon assimilation. The subcellular
localisation of StDPE2 was re-addressed in parallel with DPE2 from Arabidopsis thaliana by transient expression of yellow fluorescent protein fusions in tobacco. No translocation to the chloroplasts was observed
for any of the fusion proteins, supporting a cytosolic role of the StDPE2 enzyme in leaf starch metabolism, as has been observed
for Arabidopsis DPE2. It is concluded that StDPE1 and StDPE2 have individual essential roles in starch metabolism in potato and consequently
repression of these disables regulation of leaf malto-oligosaccharides, starch content and photosynthetic activity and thereby
plant growth possibly by a negative feedback mechanism. 相似文献
103.
Wickström SA Lange A Hess MW Polleux J Spatz JP Krüger M Pfaller K Lambacher A Bloch W Mann M Huber LA Fässler R 《Developmental cell》2010,19(4):574-588
Caveolae are specialized compartments of the plasma membrane that are involved in signaling, endocytosis, and cholesterol transport. Their formation requires the transport of caveolin-1 to the plasma membrane, but the molecular mechanisms regulating the transport are largely unknown. Here, we?identify a critical role for adhesion-mediated signaling through β1 integrins and integrin-linked kinase (ILK) in caveolae formation. Mice lacking β1 integrins or ILK in keratinocytes have dramatically reduced numbers of plasma membrane caveolae in?vivo, which is due to impaired transport of caveolin-1-containing vesicles along microtubules (MT) to the plasma membrane. Mechanistically, ILK promotes the recruitment of the F-actin binding protein IQGAP1 to the cell cortex, which, in turn, cooperates with its?effector mDia1 to locally stabilize MTs and to allow?stable insertion of caveolae into the plasma membrane. Our results assign an important role to the integrin/ILK complex for caveolar trafficking to the cell surface. 相似文献
104.
105.
Single-node leaf-bud cuttings of Schefflera arboricola Hayata and Stephanotis floribunda Brongn. were set and root formation, onset of axillary bud growth and plant height were measured. An increase in the number of roots in Schefflera, which was achieved with increasing cutting position on the stock plant (measured from top to base) or with increasing stem length below the node, accelerated the onset of axillary bud growth and resulted in an increase in plant height. Increasing the number of roots per cutting in Stephanotis through an increase in basal temperature also accelerated bud and shoot growth. Positional effects on root formation in Stephanotis showed no relationship with axillary bud growth and plant height. A positive relationship between number of roots per cutting and axillary bud growth was found among clones of Stephanotis . In general the results suggest that, with some exceptions, the onset of axillary bud growth is accelerated in cuttings as a result of accelerated root formation and a higher number of roots per cutting. 相似文献
106.
A UV-B exclusion-experiment was conducted in the high Arctic Zackenberg, NE Greenland, in which Salix arctica leaves during most of the growing season were fixed perpendicular to the solar zenith angle, thereby receiving maximal solar radiation. Covered with Teflon and Mylar foil, the leaves received approximately 90 and 40% of the ambient UV-B irradiance, respectively. The effects were examined through recordings of chlorophyll a fluorescence transients, determination of biomass and analysis of total carbon and nitrogen content and amount of soluble flavonoids in the leaves. The processing of light was analysed by means of the chlorophyll a fluorescence transient, using the so-called JIP test, as evolved by Reto J. Strasser and his coworkers. Reduction of the UV-B irradiance caused a rise in many of the fluorescence parameters during July, but not in August (late season). Thus increases in the efficiency that an absorbed photon will be trapped by the PSII reaction centre with the resultant reduction of QA to QA– (ET0/ABS = FV/FM) and the efficiency that an electron residing on QA– will enter the intersystem electron transport chain (ET0/TR0) were observed in reduced UV-B. Moreover, estimated per cross-section of leaf sample, the number of active PSII reaction centres (RC/CSM) and electron transport rate (ETM/CSM) and all performance indexes (PIABS, PICSo and PICSm) were increased in reduced UV-B. The total soluble flavonoid content was highest in ambient UV-B. The treatment effects on fluorescence parameters that were directly measured (e.g. F0 and FM) and those that were derived (e.g. quantum efficiencies, parameters per PSII reaction centres and per cross-section of leaf sample) are discussed in relation to one another, in relation to daily and seasonal variation, and from the perspective of evaluating the relative importance of UV-B of donor and acceptor side capacity in Photosystem II. In conclusion, the experimental set-up and non-invasive measurements proved to be a sensitive method to screen for effects of UV-B stress. 相似文献
107.
Primates adopt diverse hand postures during terrestrial and above-branch quadrupedal locomotion--knuckle-walking, digitigrady, and palmigrady--that incorporate varying degrees of wrist dorsiflexion (i.e., extension). Although relationships between hand postures, wrist joint range of motion, and the external properties of wrist bones (e.g., surface morphology) have been examined, the relationship between hand postures and the internal properties of wrist bones (e.g., bone density) remains largely unexplored. Because articular joint surfaces transmit mechanical loads between conjoining limb bones, measures of density (e.g., magnitudes and patterns) in the subchondral cortical plate of bone of the distal radius can be used to evaluate load regimes experienced by the wrist joint in different hand postures. We assessed apparent (i.e. optical) density patterns in several extant catarrhine primate taxa partitioned into different hand posture groups: knuckle-walking apes, digitigrade monkeys, and palmigrade monkeys. Computed tomography osteoabsorptiometry (CT-OAM) was used to construct maximum intensity projection (MIP) maps of apparent densities. High apparent density areas were characterized relative to a dorsal-volar reference plane and compared across hand posture groups. All groups had large percentage areas of high apparent density in the dorsal region of the distal radial articular surface. Only knuckle-walking apes, however, had a large percentage area of high apparent density in the volar region of the distal radial articular surface. These patterns are consistent with radiocarpal articulations in specific hand postures as evidenced by available radiographic data and suggest that the different habitual hand postures adopted by monkeys and African apes during quadrupedal locomotion have different stereotypic loading patterns. This has implications for understanding the functional morphology and evolution of knuckle-walking and digitigrade hand postures in primates. 相似文献
108.
Hansen RK Christensen C Korshunova I Kriebel M Burkarth N Kiselyov VV Olsen M Ostergaard S Holm A Volkmer H Walmod PS Berezin V Bock E 《Journal of neurochemistry》2007,103(4):1396-1407
A combinatorial library of undecapeptides was produced and utilized for the isolation of peptide binding to the fibronectin type 3 modules (F3I–F3II) of the neural cell adhesion molecule (NCAM). The isolated peptides were sequenced and produced as dendrimers. Two of the peptides (denoted ENFIN2 and ENFIN11) were confirmed to bind to F3I–F3II of NCAM by surface plasmon resonance. The peptides induced neurite outgrowth in primary cerebellar neurons and PC12E2 cells, but had no apparent neuroprotective properties. NCAM is known to activate different intracellular pathways, including signaling through the fibroblast growth factor receptor, the Src-related non-receptor tyrosine kinase Fyn, and heterotrimeric G-proteins. Interestingly, neurite outgrowth stimulated by ENFIN2 and ENFIN11 was independent of signaling through fibroblast growth factor receptor and Fyn, but could be inhibited with pertussis toxin, an inhibitor of certain heterotrimeric G-proteins. Neurite outgrowth induced by trans- homophilic NCAM was unaffected by the peptides, whereas knockdown of NCAM completely abrogated ENFIN2- and ENFIN11-induced neuritogenesis. These observations suggest that ENFIN2 and ENFIN11 induce neurite outgrowth in an NCAM-dependent manner through G-protein-coupled signal transduction pathways. Thus, ENFIN2 and ENFIN11 may be valuable for exploring this particular type of NCAM-mediated signaling. 相似文献
109.
Koski MK Hieta R Böllner C Kivirikko KI Myllyharju J Wierenga RK 《The Journal of biological chemistry》2007,282(51):37112-37123
Prolyl 4-hydroxylases (P4Hs) are 2-oxoglutarate dioxygenases that catalyze the hydroxylation of peptidyl prolines. They play an important role in collagen synthesis, oxygen homeostasis, and plant cell wall formation. We describe four structures of a P4H from the green alga Chlamydomonas reinhardtii, two of the apoenzyme at 1.93 and 2.90 A resolution, one complexed with the competitive inhibitor Zn2+, and one with Zn2+ and pyridine 2,4-dicarboxylate (which is an analogue of 2-oxoglutarate) at 1.85 A resolution. The structures reveal the double-stranded beta-helix core fold (jellyroll motif), typical for 2-oxoglutarate dioxygenases. The catalytic site is at the center of an extended shallow groove lined by two flexible loops. Mutagenesis studies together with the crystallographic data indicate that this groove participates in the binding of the proline-rich peptide-substrates. It is discussed that the algal P4H and the catalytic domain of collagen P4Hs have notable structural similarities, suggesting that these enzymes form a separate structural subgroup of P4Hs different from the hypoxia-inducible factor P4Hs. Key structural differences between these two subgroups are described. These studies provide first insight into the structure-function relationships of the collagen P4Hs, which unlike the hypoxia-inducible factor P4Hs use proline-rich peptides as their substrates. 相似文献
110.
betaIV spectrin is recruited to axon initial segments and nodes of Ranvier by ankyrinG 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
High densities of ion channels at axon initial segments (AISs) and nodes of Ranvier are required for initiation, propagation, and modulation of action potentials in axons. The organization of these membrane domains depends on a specialized cytoskeleton consisting of two submembranous cytoskeletal and scaffolding proteins, ankyrinG (ankG) and betaIV spectrin. However, it is not known which of these proteins is the principal organizer, or if the mechanisms governing formation of the cytoskeleton at the AIS also apply to nodes. We identify a distinct protein domain in betaIV spectrin required for its localization to the AIS, and show that this domain mediates betaIV spectrin's interaction with ankG. Dominant-negative ankG disrupts betaIV spectrin localization, but does not alter endogenous ankG or Na(+) channel clustering at the AIS. Finally, using adenovirus for transgene delivery into myelinated neurons, we demonstrate that betaIV spectrin recruitment to nodes of Ranvier also depends on binding to ankG. 相似文献