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951.
Elisabetta Menna Andrea Disanza Cinzia Cagnoli Ursula Schenk Giuliana Gelsomino Emanuela Frittoli Maud Hertzog Nina Offenhauser Corinna Sawallisch Hans-Jürgen Kreienkamp Frank B. Gertler Pier Paolo Di Fiore Giorgio Scita Michela Matteoli 《PLoS biology》2009,7(6)
The regulation of filopodia plays a crucial role during neuronal development and synaptogenesis. Axonal filopodia, which are known to originate presynaptic specializations, are regulated in response to neurotrophic factors. The structural components of filopodia are actin filaments, whose dynamics and organization are controlled by ensembles of actin-binding proteins. How neurotrophic factors regulate these latter proteins remains, however, poorly defined. Here, using a combination of mouse genetic, biochemical, and cell biological assays, we show that genetic removal of Eps8, an actin-binding and regulatory protein enriched in the growth cones and developing processes of neurons, significantly augments the number and density of vasodilator-stimulated phosphoprotein (VASP)-dependent axonal filopodia. The reintroduction of Eps8 wild type (WT), but not an Eps8 capping-defective mutant, into primary hippocampal neurons restored axonal filopodia to WT levels. We further show that the actin barbed-end capping activity of Eps8 is inhibited by brain-derived neurotrophic factor (BDNF) treatment through MAPK-dependent phosphorylation of Eps8 residues S624 and T628. Additionally, an Eps8 mutant, impaired in the MAPK target sites (S624A/T628A), displays increased association to actin-rich structures, is resistant to BDNF-mediated release from microfilaments, and inhibits BDNF-induced filopodia. The opposite is observed for a phosphomimetic Eps8 (S624E/T628E) mutant. Thus, collectively, our data identify Eps8 as a critical capping protein in the regulation of axonal filopodia and delineate a molecular pathway by which BDNF, through MAPK-dependent phosphorylation of Eps8, stimulates axonal filopodia formation, a process with crucial impacts on neuronal development and synapse formation. 相似文献
952.
Daniel Voß Susanne Pfefferle Christian Drosten Lea Stevermann Elisabetta Traggiai Antonio Lanzavecchia Stephan Becker 《Virology journal》2009,6(1):1-13
Background
Dengue is the most important arbovirus disease in tropical and subtropical countries. The viral envelope (E) protein is responsible for cell receptor binding and is the main target of neutralizing antibodies. The aim of this study was to analyze the diversity of the E protein gene of DENV-3. E protein gene sequences of 20 new viruses isolated in Ribeirao Preto, Brazil, and 427 sequences retrieved from GenBank were aligned for diversity and phylogenetic analysis.Results
Comparison of the E protein gene sequences revealed the presence of 47 variable sites distributed in the protein; most of those amino acids changes are located on the viral surface. The phylogenetic analysis showed the distribution of DENV-3 in four genotypes. Genotypes I, II and III revealed internal groups that we have called lineages and sub-lineages. All amino acids that characterize a group (genotype, lineage, or sub-lineage) are located in the 47 variable sites of the E protein.Conclusion
Our results provide information about the most frequent amino acid changes and diversity of the E protein of DENV-3. 相似文献953.
Elisabetta Schievano Laura Silvestri Marina Gobbo Stefano Mammi Raniero Rocchi Evaristo Peggion 《Journal of peptide science》2005,11(1):3-16
The conformational properties in DMSO of two head-to-tail cyclic analogues of kallidin ([Lys(0)]-bradykinin, KL) as well as those of the corresponding linear peptides were studied by NMR and molecular dynamics (MD) simulations. The modifications in the sequence were introduced at position 6, resulting in the four peptides, [Tyr(6)]-KL (YKL), [Trp(6)]-KL (WKL), cyclo-([Tyr(6)]-KL) (YCKL) and cyclo-([Trp(6)]-KL) (WCKL).The linear WKL analogue was significantly more potent than kallidin on rat duodenum preparations, whereas YKL was significantly less potent. Both cyclic peptides, YCKL and WCKL displayed similar activity, lower than that of the linear analogues and also of cyclo-KL.The two linear analogues display high conformational flexibility in DMSO. In the predominant conformer, for both peptides, all three X-Pro bonds adopt a trans configuration. Three out of four conformers present in YCKL and WCKL were completely assigned. The configurations at the X-Pro bonds are the same for the two analogues. All cyclic conformers show a cis configuration in at least one X-Pro bond and always opposite configuration for the two consecutive X-Pro bonds.The NOE-restrained MD calculations resulted in the detection of several elements of secondary structure in each of the conformers. Such elements are described and their possible relevance to biological activity is discussed. 相似文献
954.
Letter to the editor: Reply to Hardy & Buckley: Earliest evidence of bitumen from Homo sp. teeth is from El Sidro'n 下载免费PDF全文
Gregorio Oxilia Flavia Fiorillo Francesco Boschin Elisabetta Boaretto Salvatore A. Apicella Chiara Matteucci Daniele Panetta Rossella Pistocchi Franca Guerrini Cristiana Margherita Massimo Andretta Rita Sorrentino Giovanni Boschian Simona Arrighi Irene Dori Giuseppe Mancuso Jacopo Crezzini Alessandro Riga Maria C. Serrangeli Antonino Vazzana Piero A. Salvadori Mariangela Vandini Carlo Tozzi Adriana Moroni Robin N. M. Feeney John C. Willman Jacopo Moggi‐Cecchi Stefano Benazzi 《American journal of physical anthropology》2017,164(1):214-215
955.
PPARα Antagonist AA452 Triggers Metabolic Reprogramming and Increases Sensitivity to Radiation Therapy in Human Glioblastoma Primary Cells 下载免费PDF全文
Elisabetta Benedetti Michele d'Angelo Alessandra Ammazzalorso Giovanni Luca Gravina Chiara Laezza Andrea Antonosante Gloria Panella Benedetta Cinque Loredana Cristiano Anne Chloè Dhez Carlo Astarita Renato Galzio Maria Grazia Cifone Rodolfo Ippoliti Rosa Amoroso Ernesto Di Cesare Antonio Giordano Annamaria Cimini 《Journal of cellular physiology》2017,232(6):1458-1466
956.
Cristian Ascione Arianna Sala Elham Mazaheri-Tehrani Simona Paulone Beniamino Palmieri Elisabetta Blasi Claudio Cermelli 《Annals of clinical microbiology and antimicrobials》2017,16(1):72
Background
Recently, we published data suggesting a mutualistic relationship between HSV-1 and Candida. albicans; in particular: (a) HSV-1 infected macrophages are inhibited in their anti-Candida effector function and (b) Candida biofilm protects HSV-1 from inactivation. The present in vitro study is aimed at testing the effects of Candida biofilm on HSV-1 sensitivity to pharmacological and physical stress, such as antiviral drugs (acyclovir and foscarnet) and laser UVA1 irradiation. We also investigated whether fungus growth pattern, either sessile or planktonic, influences HSV-1 sensitivity to antivirals.Methods
Mature Candida biofilms were exposed to HSV-1 and then irradiated with laser light (UVA1, 355 λ). In another set of experiments, mature Candida biofilm were co-cultured with HSV-1 infected VERO cells in the presence of different concentrations of acyclovir or foscarnet. In both protocols, controls unexposed to laser or drugs were included. The viral yield of treated and untreated samples was evaluated by end-point titration. To evaluate whether this protective effect might occur in relation with a different growth pattern, HSV-1 infected cells were co-cultured with either sessile or planktonic forms of Candida and then assessed for susceptibility to antiviral drugs.Results
UVA1 irradiation caused a 2 Log reduction of virus yield in the control cultures whereas the reduction was only 1 Log with Candida biofilm, regardless to the laser dose applied to the experimental samples (50 or 100 J/cm2). The presence of biofilm increased the IC90 from 18.4–25.6 J/cm2. Acyclovir caused a 2.3 Log reduction of virus yield in the control cultures whereas with Candida biofilm the reduction was only 0.5 Log; foscarnet determined a reduction of 1.4 Log in the controls and 0.2 Log in biofilm cultures. Consequently, the ICs50 for acyclovir and foscarnet increased by 4- and 12-folds, respectively, compared to controls. When HSV-1 was exposed to either sessile or planktonic fungal cells, the antiviral treatments caused approximately the same weak reduction of virus yield.Conclusions
These data demonstrate that: (1) HSV-1 encompassed in Candida biofilm is protected from inactivation by physical (laser) and pharmacological (acyclovir or foscarnet) treatments; (2) the drug antiviral activity is reduced at a similar extent for both sessile or planktonic Candida.957.
Structural intermediates in the fusion‐associated transition of vesiculovirus glycoprotein 下载免费PDF全文
Hélène Raux Abbas Abou‐Hamdan Elisabetta Boeri‐Erba Malika Ouldali Linda Buonocore John K Rose Jean Lepault Stéphane Bressanelli Yves Gaudin 《The EMBO journal》2017,36(5):679-692
Vesiculoviruses enter cells by membrane fusion, driven by a large, low‐pH‐induced, conformational change in the fusion glycoprotein G that involves transition from a trimeric pre‐fusion toward a trimeric post‐fusion state via monomeric intermediates. Here, we present the structure of the G fusion protein at intermediate pH for two vesiculoviruses, vesicular stomatitis virus (VSV) and Chandipura virus (CHAV), which is responsible for deadly encephalopathies. First, a CHAV G crystal structure shows two intermediate conformations forming a flat dimer of heterodimers. On virions, electron microscopy (EM) and tomography reveal monomeric spikes similar to one of the crystal conformations. In solution, mass spectrometry shows dimers of G. Finally, mutations at a dimer interface, involving fusion domains associated in an antiparallel manner to form an intermolecular β‐sheet, affect G fusion properties. The location of the compensatory mutations restoring fusion activity strongly suggests that this interface is functionally relevant. This work reveals the range of G structural changes and suggests that G monomers can re‐associate, through antiparallel interactions between fusion domains, into dimers that play a role at some early stage of the fusion process. 相似文献
958.
Francesco Rovero Nisha Owen Trevor Jones Elisabetta Canteri Aaron Iemma Clara Tattoni 《Biodiversity and Conservation》2017,26(5):1103-1119
Large-bodied mammals are a rich and diversified faunal group in tropical rainforests. However, knowledge on community size and composition, and on species’ distribution and ecology remains often scant and inadequate against their chronic status of threats. We used camera trapping to detect mammals in the forests of the Eastern Arc Mountains (EAM) of Tanzania, a world renowned region for biodiversity comprised by a series of distinct and ancient mountain ranges partially covered in moist montane forest. We conducted surveys from 2003 to 2011 in eight of the 12 mountain blocks in Tanzania, and, through an overall sampling effort of 11,500 camera days, we detected 43 species. We normalized species richness and species’ detection events by effort, and used these metrics to assess the effect of habitat and human disturbance variables. We found that rarefied richness is positively affected by forest area at the block level, and that richness at forest patch level is also affected by forest area as well as surrounding human density (negative effect). For a subset of 17 species, we found consistent patterns of avoidance or tolerance of human disturbance and forest edges, and increased occurrence in areas at higher elevation, matching the historical forest loss that in most mountains occurred at lower elevation. Our study provides ecological insights that are novel for most species and sites, and reveals a general trend of negative impact of human disturbance on both community size and species’ relative abundance. Increased protection of the EAM forests in Tanzania is of urgent importance for the persistence of diversified mammal communities. 相似文献
959.
Pastorini E Locatelli M Simoni P Roda G Roda E Roda A 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2008,872(1-2):99-106
A new HPLC method for the determination of 5-aminosalicylic acid (5-ASA) and N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) in human plasma was developed and validated. Plasma samples were analyzed after protein precipitation with methanol and the two analytes were separated using a C18 column with a mobile phase composed of 17.5mmol/L acetic acid (pH 3.3):acetonitrile=85:15 (v/v) at 0.2mL/min flow rate. 4-ASA and N-Ac-4-ASA were used as internal standards. Selective detection was performed by tandem mass spectrometry with electrospray source, operating in negative ionization mode and in multiple reaction monitoring acquisition (m/z 152-->108 for 5-ASA; m/z 194-->150 and 194-->107 for N-Ac-5-ASA). The limit of quantification (LOQ) was 50ng/mL for both analytes (0.2ng injected) and matrix-matched standard curves showed linearity up to 4000ng/mL. In the entire analytical range the within- and between-batch precision (R.S.D.%) values were respectively =6.3% and =11% for 5-ASA and =8.0% and =10% for N-Ac-5-ASA. For both analytes the within- and between-batch accuracy (bias%) values ranged respectively from -8.4% to 7.9% and from -7.9% to 8.0%. The overall recoveries (n=6) at three tested concentration levels (i.e. 100, 1000 and 4000ng/mL) were respectively >90% for 5-ASA and >95% for N-Ac-5-ASA (R.S.D.%=10%). The method was applied to evaluate the pharmacokinetic of 5-ASA after a single oral dose administration of this compound (1200mg) to 24 healthy volunteers. The mean maximum concentration levels were 680ng/mL for 5-ASA and 1240ng/mL for N-Ac-5-ASA and the kinetic profiles were in agreement with previous studies. 相似文献
960.