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71.
Ribosomal protein S14 genes (RPS14) in eukaryotic species from protozoa to
primates exhibit dramatically different intron-exon structures yet share
homologous polypeptide-coding sequences. To recognize common features of
RPS14 gene architectures in closely related mammalian species and to
evaluate similarities in their noncoding DNA sequences, we isolated the
intron-containing S14 locus from Chinese hamster ovary (CHO) cell DNA by
using a PCR strategy and compared it with human RPS14. We found that rodent
and primate S14 genes are composed of identical protein-coding exons
interrupted by introns at four conserved DNA sites. However, the structures
of corresponding CHO and human RPS14 introns differ significantly.
Nonetheless, individual intron splice donor, splice acceptor, and upstream
flanking motifs have been conserved within mammalian S14 homologues as well
as within RPS14 gene fragments PCR amplified from other vertebrate genera
(birds and bony fish). Our data indicate that noncoding, intronic DNA
sequences within highly conserved, single-copy ribosomal protein genes are
useful molecular landmarks for phylogenetic analysis of closely related
vertebrate species.
相似文献
72.
George?M?WarimweEmail author Gema?Lorenzo Elena?Lopez-Gil Arturo?Reyes-Sandoval Matthew?G?Cottingham Alexandra?J?Spencer Katharine?A?Collins Matthew?DJ?Dicks Anita?Milicic Amar?Lall Julie?Furze Alison?V?Turner Adrian?VS?Hill Alejandro?Brun Sarah?C?Gilbert 《Virology journal》2013,10(1):349
Background
Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens.Methods
Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice.Results
A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8+ T cell response.Conclusions
Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.73.
74.
This article selectively reviews research concerning nicotine's effects on cognition, including the neurobiological mechanism for these effects, task and experimental features that may be important for elucidating these effects, and why these effects may have amplified motivational significance among smokers with cognitive deficit. Nicotine has effects on various cognitive processes, though most studies in humans have focused on the amelioration of cognitive deficits experienced during drug withdrawal. The direct cognitive-enhancing effect of nicotine remains a controversial topic. The relationship between attentional and non-attentional cognitive effects of nicotine is discussed in the context of cognitive self-medication. Further research should include theory-driven examination of cognitive effects of nicotine, and develop targeted smoking cessation programs based on an improved understanding of the role of cognitive self-medication in high-risk individuals. 相似文献
75.
Fu Y Nitecki DE Maltby D Simon GH Berejnoi K Raatschen HJ Yeh BM Shames DM Brasch RC 《Bioconjugate chemistry》2006,17(4):1043-1056
The purpose of this study was to design, synthesize, and initially characterize a representative set of novel constructs for large-molecular radiographic/computed tomography (CT) contrast agents, intended for a primarily intravascular distribution. A new assembly of well-known and biocompatible components consists of paired, symmetrical dendritic polylysines initiated from both ends of a poly(ethylene glycol) (PEG) core, yielding an array of multiple free amino groups to which were conjugated highly soluble and stable triiodophthalamide ("triiodo") moieties. An array of six dendritic contrast agents was synthesized originally, using three different PEG cores (3, 6, 12 kDa) with t-Boc lysine-generated dendrimer "amplifiers" (from three to five generations) containing 16 to 64 amino groups for conjugation with reactive triiodo moieties. A clinically used, nonionic, small molecular CT contrast agent, iobitridol, was derivatized via a hydroxyl protection/deprotection strategy, introducing a new carboxyl group available for conjugation to the lysine amino groups of dendrimers. Final products were purified by size exclusion chromatography and characterized by NMR, UV, HPLC, and elemental analysis. Preliminary evaluations were conducted for physicochemical characterization and in vivo CT contrast enhancement in a rat model. All six iodinated PEG-core dendrimer conjugates were synthesized in good yields, with a high degree of size monodispersity, large apparent molecular weight, favored physicochemical properties. A representative compound, PEG12000-carbamate-Gen4-IOB conjugate, 27% (w%) rich in iodine, demonstrated a desirable strong and persistent intravascular enhancement with a monoexponential blood half-life of approximately 35 min assayed by dynamic CT imaging and also showed high water solubility (>550 mg/mL at 25 degrees C), large apparent molecular size (comparable to a 143-kDa protein), high hydrophilicity (butanol-water partition coefficient 0.015), and stability to autoclaving conditions. This study showed the synthetic feasibility, desired basic characteristics, and potential utility for CT contrast enhancement achieved with a new type of iodinated, large-molecular PEG-core dendritic construct. Further development of this class of macromolecular contrast agents will be required to define the optimal formulation, pharmacology, safety profile, and the full range of diagnostic applications including tumor microvascular quantitative characterization by CT imaging. 相似文献
76.
Fiona H. Fry Brenda Dougan Anthony C. Willis Nicola E. Brasch 《Inorganica chimica acta》2008,361(8):2321-2326
Despite the importance of VIII in biology, only three VIII complexes of naturally occurring amino acids have been structurally characterized. We report the structure of the first vanadium complex incorporating a glycine ligand, [V(Gly)3] · 2DMSO, which crystallizes in a monoclinic system with space group Cc, a = 8.9186(5) Å, b = 21.5347(9) Å, c = 9.9064(5) Å and β = 110.536(3)°. The X-ray structural data show the central VIII metal octahedrally coordinated by three bidentate glycinato ligands arranged a mer configuration, with both Δ and Λ enantiomers present in the unit cell. The bulk sample was isolated as [V(Gly)3] · DMSO · NaCl. Structural comparisons are made with the corresponding homoleptic glycinato complexes of CoIII, CrIII and NiII. The structure of trans-[V(OH2)4Cl2]Cl · 2H2O has also been re-determined. This latter complex crystallizes in a monoclinic system in the P2(1)/c space group, a = 6.4381(9) Å, b = 6.3843(9) Å, c = 11.7980(17) Å and β = 98.057(2)°. The vanadium atom lies at a crystallographic inversion centre within the distorted octahedron formed by the four water and two chloride ligands. 相似文献
77.
Andrew C Doxey Michael DJ Lynch Kirsten M Müller Elizabeth M Meiering Brendan J McConkey 《BMC evolutionary biology》2008,8(1):316
Background
Clostridial neurotoxins (CNTs) are the most deadly toxins known and causal agents of botulism and tetanus neuroparalytic diseases. Despite considerable progress in understanding CNT structure and function, the evolutionary origins of CNTs remain a mystery as they are unique to Clostridium and possess a sequence and structural architecture distinct from other protein families. Uncovering the origins of CNTs would be a significant contribution to our understanding of how pathogens evolve and generate novel toxin families. 相似文献78.
S. N. Suresh Aravinda K. Chavalmane Vidyadhara DJ Haorei Yarreiphang Shashank Rai Abhik Paul 《Autophagy》2017,13(7):1221-1234
Parkinson disease (PD) is a life-threatening neurodegenerative movement disorder with unmet therapeutic intervention. We have identified a small molecule autophagy modulator, 6-Bio that shows clearance of toxic SNCA/α-synuclein (a protein implicated in synucleopathies) aggregates in yeast and mammalian cell lines. 6-Bio induces autophagy and dramatically enhances autolysosome formation resulting in SNCA degradation. Importantly, neuroprotective function of 6-Bio as envisaged by immunohistology and behavior analyses in a preclinical model of PD where it induces autophagy in dopaminergic (DAergic) neurons of mice midbrain to clear toxic protein aggregates suggesting that it could be a potential therapeutic candidate for protein conformational disorders. 相似文献
79.
Cultured rat schwann cells grown in association with sensory neurons when labeled with [(3)H]leucinem, [(3)H]glucosamine, or [(35)S]methionine release labeled polypeptides into the culture medium. Analysis by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) of the culture medium reveals a reproducible pattern of more than 20 polypeptides with molecular weights ranging from 15,000 to more than 250,000. Five major polypeptides (apparent molecular weights 225,000, 210,000, 90,000, 66,000, 50,000, and 40,000) account for approximately 40 percent of the leucine or methionine radioactivity in medium polypeptide. Schwann cells grown in a serum-free defined medium, in which schwann cells do not relate normally to axons, release approximately four times less labeled medium polypeptides tha cultures grown in medium supplemented with serum and chick embryo extract. In addition, there is a qualitative difference in the pattern of medium polypeptides resolved by SDS-PAGE, so that a single polypeptide (mol wt 40,000) accounts for nearly all of the label in medium polypeptides. Switching of cultures grown in defined medium to supplemented medium for 2 d results in a fourfold increase in the amount of labeled polypeptides appearing in the culture medium, and a return to the normal pattern of medium polypeptides appearing in the culture medium, and a return to the normal pattern of medium polypeptides as resolved by SDS-PAGE. This change in the pattern of polypeptides release by schwann cells is accompanied by changes in the association between schwann cells and axons. An early step in the establishment of normal axon-schwann cell relations appears to be an inward migration of schwann cells into axonal bundles and spreading of schwann cells along neurites. These changes are evident within 48 h after medium shift. Our results thus suggest that the release of proteins by schwann cells may be important for the development of normal axonal ensheathment. 相似文献
80.
Steven G Thomas Simon DJ Calaminus Jocelyn M Auger Stephen P Watson Laura M Machesky 《BMC cell biology》2007,8(1):46