全文获取类型
收费全文 | 424篇 |
免费 | 28篇 |
出版年
2023年 | 2篇 |
2022年 | 4篇 |
2021年 | 4篇 |
2020年 | 7篇 |
2019年 | 5篇 |
2018年 | 4篇 |
2017年 | 8篇 |
2016年 | 12篇 |
2015年 | 24篇 |
2014年 | 14篇 |
2013年 | 47篇 |
2012年 | 14篇 |
2011年 | 17篇 |
2010年 | 18篇 |
2009年 | 14篇 |
2008年 | 17篇 |
2007年 | 12篇 |
2006年 | 19篇 |
2005年 | 16篇 |
2004年 | 13篇 |
2003年 | 17篇 |
2002年 | 11篇 |
2001年 | 14篇 |
2000年 | 11篇 |
1999年 | 13篇 |
1998年 | 10篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 7篇 |
1990年 | 8篇 |
1989年 | 6篇 |
1988年 | 4篇 |
1987年 | 7篇 |
1986年 | 8篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1983年 | 9篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1973年 | 1篇 |
1971年 | 1篇 |
1964年 | 3篇 |
排序方式: 共有452条查询结果,搜索用时 15 毫秒
381.
382.
383.
The two-component phosphorylation network is of critical importance for bacterial growth and physiology. Here, we address plasticity and interconnection of distinct signal transduction pathways within this network. In Caulobacter crescentus antagonistic activities of the PleC phosphatase and DivJ kinase localized at opposite cell poles control the phosphorylation state and subcellular localization of the cell fate determinator protein DivK. We show that DivK functions as an allosteric regulator that switches PleC from a phosphatase into an autokinase state and thereby mediates a cyclic di-GMP-dependent morphogenetic program. Through allosteric activation of the DivJ autokinase, DivK also stimulates its own phosphorylation and polar localization. These data suggest that DivK is the central effector of an integrated circuit that operates via spatially organized feedback loops to control asymmetry and cell fate determination in C. crescentus. Thus, single domain response regulators can facilitate crosstalk, feedback control, and long-range communication among members of the two-component network. 相似文献
384.
Grondard C Biondi O Pariset C Lopes P Deforges S Lécolle S Gaspera BD Gallien CL Chanoine C Charbonnier F 《Journal of cellular physiology》2008,214(1):126-135
This study establishes a causal link between the limitation of myofibre transitions and modulation of calcineurin activity, during different exercise paradigms. We have designed a new swimming-based training protocol in order to draw a comparison between a high frequency and amplitude exercise (swimming) and low frequency and amplitude exercise (running). We initially analysed the time course of muscle adaptations to a 6- or 12-week swimming- or running-based training exercise program, on two muscles of the mouse calf, the slow-twitch soleus and the fast-twitch plantaris. The magnitude of exercise-induced muscle plasticity proved to be dependent on both the muscle type and the exercise paradigm. In contrast to the running-based training which generated a continuous increase of the slow phenotype throughout a 12-week training program, swimming induced transitions to a slower phenotype which ended after 6 weeks of training. We then compared the time course of the exercise-induced changes in calcineurin activity during muscle adaptation to training. Both exercises induced an initial activation followed by the inhibition of calcineurin. In the muscles of animals submitted to a 12-week swimming-based training, this inhibition was concomitant with the end of myofibre transition. Calcineurin inhibition was a consequence of the inhibition of its catalytic subunit gene expression on one hand, and of the expression increase of the modulatory calcineurin interacting proteins 1 gene (MCIP1), on the other. The present study provides the first experimental cues for an interpretation of muscle phenotypic variation control. 相似文献
385.
386.
Is supercomplex organization of the respiratory chain required for optimal electron transfer activity? 总被引:1,自引:0,他引:1
Genova ML Baracca A Biondi A Casalena G Faccioli M Falasca AI Formiggini G Sgarbi G Solaini G Lenaz G 《Biochimica et biophysica acta》2008,1777(7-8):740-746
The supra-molecular assembly of the main respiratory chain enzymatic complexes in the form of "super-complexes" has been proved by structural and functional experimental evidence. This evidence strongly contrasts the previously accepted Random Diffusion Model stating that the complexes are functionally connected by lateral diffusion of small redox molecules (i.e. Coenzyme Q and cytochrome c). This review critically examines the available evidence and provides an analysis of the functional consequences of the intermolecular association of the respiratory complexes pointing out the role of Coenzyme Q and of cytochrome c as channeled or as freely diffusing intermediates in the electron transfer activity of their partner enzymes. 相似文献
387.
Adenylyl Cyclase/cAMP System Involvement in the Antiangiogenic Effect of Somatostatin in the Retina. Results from Transgenic Mice 总被引:1,自引:0,他引:1
Ristori C Ferretti ME Pavan B Cervellati F Casini G Catalani E Dal Monte M Biondi C 《Neurochemical research》2008,33(7):1247-1255
Neoangiogenesis is a response to retinal hypoxia that is inhibited by somatostatin (SRIF) through its subtype 2 receptor (sst2). Using a mouse model of hypoxia-induced retinopathy, we investigated whether inhibition of adenylyl cyclase (AC) is involved in SRIF anti-angiogenic actions. Hypoxia increased AC responsiveness in wild type (WT) retinas and in retinas lacking sst2, but not in sst2-overexpressing retinas. Hypoxia also altered AC isoform expression with different patterns depending on sst2 expression level. The AC VII isoform mRNA and protein resulted the most affected. Indeed, in hypoxia AC VII expression was enhanced in WT retinas and it was further increased in sst2-lacking retinas, whereas in sst2 overexpressing retinas the increase of AC VII was lower than in WT retinas. These data suggest an involvement of AC/cAMP in mediating both hypoxia-evoked retinal neoangiogenesis and SRIF protective actions. The AC VII isoform is a candidate to a main role in these mechanisms. 相似文献
388.
Goetz Benndorf Mircea Ionescu Miguel Valdivia y Alvarado Alessandra Biondi John Hipp Ralph Metcalfe 《Journal of biomechanics》2010,43(4):740-748
Previous research on the effects of intracranial stents on arterial hemodynamics has involved computational hemodynamics (CHD) simulations applied to artificially generated stent models. In this study, accurate geometric reconstructions of in-vitro (PTFE tube) and ex-vivo (canine artery) deployed stents based on ultra-high resolution MicroCT imaging were used. The primary goal was to compare the hemodynamic effects of deployment in these two different models and to identify flow perturbations due to deployment anomalies such as stent malapposition and strut prolapse, important adverse mechanics occurring in clinical practice, but not considered in studies using idealized stent models.Ultra-high resolution MicroCT data provided detailed visualization of deployment characteristics allowing for accurate in-stent flow simulation. For stent cells that are regularly and symmetrically deployed, the near wall flow velocities and wall shear stresses were similar to previously published results derived from idealized models. In-stent hemodynamics were significantly altered by misaligned or malapposed stent cells, important effects not realistically captured in previous models. This research shows the feasibility and value of an ex-vivo stent model for MicroCT based CHD studies. It validates previous in-vitro studies and further contributes to the understanding of in-stent hemodynamics associated with adverse mechanics of self-expanding intracranial stents. 相似文献
389.
Novel glycosylated VIP analogs: synthesis, biological activity, and metabolic stability. 总被引:1,自引:0,他引:1
David Dangoor Barbara Biondi Marina Gobbo Yelena Vachutinski Mati Fridkin Illana Gozes Raniero Rocchi 《Journal of peptide science》2008,14(3):321-328
Vasoactive intestinal peptide (VIP) is a prominent neuropeptide, exhibiting a wide spectrum of biological activities in mammals. However, the clinical applications of VIP are mainly hampered because of its rapid degradation in vivo. Peptide glycosylation, a procedure frequently used to increase peptide resistance to proteolytic degradation and consequently increase peptide metabolic stability, has not been performed yet on VIP. The presence of three N-glycosylation sites on VIP receptor type 1 (VPAC1) was previously demonstrated. Therefore, glycosylation of the VIP ligand could potentially increase its receptor affinity because of glyco-glyco interactions between the ligand and the receptor. In order to enhance VIP's metabolic stability and to increase its ligand-receptor binding/activation, eight glycosylated VIP derivatives were successfully synthesized by the solid-phase procedure. Each VIP analog was monoglycosylated by a monosaccharide addition to one amino-acid residue along the sequence. Glycosylation did not affect the alpha-helical structure shown by the native VIP in organic environment. Few glycosylated VIP analogs displayed highly potent VPAC1 receptor binding and cAMP-induced activation; only 4-6 fold lower in comparison to the native VIP. Furthermore, the peptide analog glycosylated on Thr11 ([11Glyc]VIP) showed a significantly enhanced stability toward trypsin enzymatic degradation in comparison to VIP. Analysis of the degradation products of [11Glyc]VIP showed that differently from VIP, incubation of the peptide [11Glyc]VIP with trypsin resulted in no cleavage at the Arg12-Leu13 peptide bond, suggesting that VIP glycosylation may lead to enhanced metabolic stability. 相似文献
390.
Fredrik RM Huss Erika Nyman Carl-Johan Gustafson Katrin Gisself?lt Elisabeth Liljensten Gunnar Kratz 《Organogenesis》2008,4(3):195-200
Full thickness skin wounds in humans heal with scars, but without regeneration of the dermis. A degradable poly(urethane urea) scaffold (PUUR), Artelon® is already used to reinforce soft tissues in orthopaedics, and for treatment of osteoarthritis of the hand, wrist and foot. In this paper we have done in vitro experiments followed by in vivo studies to find out whether the PUUR is biocompatible and usable as a template for dermal regeneration. Human dermal fibroblasts were cultured on discs of PUUR, with different macrostructures (fibrous and porous). They adhered to and migrated into the scaffolds, and produced collagen. The porous scaffold was judged more suitable for clinical applications and 4 mm Ø, 2 mm-thick discs of porous scaffold (12% w/w or 9% w/w polymer solution) were inserted intradermally in four healthy human volunteers. The implants were well tolerated and increasing ingrowth of fibroblasts was seen over time in all subjects. The fibroblasts stained immunohistochemically for procollagen and von Willebrand factor, indicating neocollagenesis and angiogenesis within the scaffolds. The PUUR scaffold may be a suitable material to use as a template for dermal regeneration.Key words: dermal regeneration, tissue engineering, polymer scaffold, wound healing, in vitro, in vivo, guided tissue regeneration, human, burns 相似文献