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131.
Trosset JY Dalvit C Knapp S Fasolini M Veronesi M Mantegani S Gianellini LM Catana C Sundström M Stouten PF Moll JK 《Proteins》2006,64(1):60-67
The interaction between beta-catenin and Tcf family members is crucial for the Wnt signal transduction pathway, which is commonly mutated in cancer. This interaction extends over a very large surface area (4800 A(2)), and inhibiting such interactions using low molecular weight inhibitors is a challenge. However, protein surfaces frequently contain "hot spots," small patches that are the main mediators of binding affinity. By making tight interactions with a hot spot, a small molecule can compete with a protein. The Tcf3/Tcf4-binding surface on beta-catenin contains a well-defined hot spot around residues K435 and R469. A 17,700 compounds subset of the Pharmacia corporate collection was docked to this hot spot with the QXP program; 22 of the best scoring compounds were put into a biophysical (NMR and ITC) screening funnel, where specific binding to beta-catenin, competition with Tcf4 and finally binding constants were determined. This process led to the discovery of three druglike, low molecular weight Tcf4-competitive compounds with the tightest binder having a K(D) of 450 nM. Our approach can be used in several situations (e.g., when selecting compounds from external collections, when no biochemical functional assay is available, or when no HTS is envisioned), and it may be generally applicable to the identification of inhibitors of protein-protein interactions. 相似文献
132.
Raoul M Patigny D Fabis F Dauphin F Rault S Sapi J Laronze JY 《Journal of enzyme inhibition and medicinal chemistry》2006,21(3):251-260
Several new 2-vinyl-Nb,Nb-dimethyltryptamines were prepared using Fischer indole synthesis followed by simple functional group transformations and evaluated on 5-HT4, 5-HT5, 5-HT6 and 5-HT7 serotonin receptors. It was found that 2-vinyl substitution conferred a potent and selective 5-HT6 binding activity to these molecules which could be enhanced by Na-arylsulfonyl substituents. 相似文献
133.
Saisongkorh W El Karkouri K Patrice JY Bernard A Rolain JM Raoult D 《FEMS immunology and medical microbiology》2012,64(1):111-114
In cell culture, Rickettsia felis grows only at low temperatures (< 31 °C). Therefore, its ability to enter, survive and grow in cell lines has primarily been tested in cells derived from amphibians and arthropods, which naturally grow at low temperatures, and only infrequently in mammalian cells. We subcultured R. felis in mammalian cells for more than 10 passages using media supplemented with tryptose phosphate broth (TPB) and found that TPB is critical for optimal growth of R. felis in mammalian cells. 相似文献
134.
Kouwen TR Dubois JY Freudl R Quax WJ van Dijl JM 《Applied and environmental microbiology》2008,74(24):7536-7545
Disulfide bonds are important for the correct folding, structural integrity, and activity of many biotechnologically relevant proteins. For synthesis and subsequent secretion of these proteins in bacteria, such as the well-known "cell factory" Bacillus subtilis, it is often the correct formation of disulfide bonds that is the greatest bottleneck. Degradation of inefficiently or incorrectly oxidized proteins and the requirement for costly and time-consuming reduction and oxidation steps in the downstream processing of the proteins still are major limitations for full exploitation of B. subtilis for biopharmaceutical production. Therefore, the present study was aimed at developing a novel in vivo strategy for improved production of secreted disulfide-bond-containing proteins. Three approaches were tested: depletion of the major cytoplasmic reductase TrxA; introduction of the heterologous oxidase DsbA from Staphylococcus carnosus; and addition of redox-active compounds to the growth medium. As shown using the disulfide-bond-containing molecule Escherichia coli PhoA as a model protein, combined use of these three approaches resulted in secretion of amounts of active PhoA that were approximately 3.5-fold larger than the amounts secreted by the parental strain B. subtilis 168. Our findings indicate that Bacillus strains with improved oxidizing properties can be engineered for biotechnological production of heterologous high-value proteins containing disulfide bonds. 相似文献
135.
Doublet B Douard G Targant H Meunier D Madec JY Cloeckaert A 《Journal of microbiological methods》2008,75(2):359-361
The Red recombinase system of bacteriophage Lambda has been used to inactivate chromosomal genes in bacteria using PCR products. In this study, we describe the replacement of the ampicillin resistance marker of helper plasmids pKD46 and pCP20 by a gentamicin resistance gene to disrupt chromosomal genes and then to eliminate FRT flanked resistance gene in multiple antibiotic-resistant Salmonella enterica strains. 相似文献
136.
Maria Luisa Brandi Luigi Gennari Marco Matucci Cerinic Lucia Becherini Alberto Falchetti Laura Masi Carlo Gennari Jean-Yves Reginster 《Arthritis research & therapy》2001,3(5):270-11
Osteoarthritis and osteoporosis are the two most common age-related chronic disorders of articular joints and skeleton, representing
a major public health problem in most developed countries. Apart from being influenced by environmental factors, both disorders
have a strong genetic component, and there is now considerable evidence from large population studies that these two disorders
are inversely related. Thus, an accurate analysis of the genetic component of one of these two multifactorial diseases may
provide data of interest for the other. However, the existence of confounding factors must always be borne in mind in interpreting
the genetic analysis. In addition, each patient must be given an accurate clinical evaluation, including family history, history
of drug treatments, lifestyle, and environment, in order to reduce the background bias. Here, we review the impact of recent
work in molecular genetics suggesting that powerful molecular biology techniques will soon make possible both a rapid accumulation
of data on the genetics of both disorders and the development of novel diagnostic, prognostic, and therapeutic approaches. 相似文献
137.
The<Emphasis Type="Italic">atspo11-1</Emphasis> mutation rescues <Emphasis Type="Italic">atxrcc3</Emphasis> meiotic chromosome fragmentation 总被引:2,自引:0,他引:2
Homologous recombination events occurring during meiotic prophase I ensure the proper segregation of homologous chromosomes at the first meiotic division. These events are initiated by programmed double-strand breaks produced by the Spo11 protein and repair of such breaks by homologous recombination requires a strand exchange activity provided by the Rad51 protein. We have recently reported that the absence of AtXrcc3, an ArabidopsisRad51 paralogue, leads to extensive chromosome fragmentation during meiosis, first visible in diplotene of meiotic prophase I. The present study clearly shows that this fragmentation results from un- or mis-repaired AtSpo11-1 induced double-strand breaks and is thus due to a specific defect in the meiotic recombination process. 相似文献
138.
Marie-Pierre Forquin Hugo Duvergey Caroline Proux Valentin Loux Jerome Mounier Sophie Landaud Jean-Yves Coppée Jean-Fran?ois Gibrat Pascal Bonnarme Isabelle Martin-Verstraete Tatiana Vallaeys 《Applied and environmental microbiology》2009,75(19):6406-6409
Multilocus sequence typing with nine selected genes is shown to be a promising new tool for accurate identifications of Brevibacteriaceae at the species level. A developed microarray also allows intraspecific diversity investigations of Brevibacterium aurantiacum showing that 13% to 15% of the genes of strain ATCC 9174 were absent or divergent in strain BL2 or ATCC 9175.Brevibacteriaceae play a major part in the cheese smear community (6, 11). The classification and typing of cheese-related Brevibacteriaceae have been based mainly on molecular methods such as amplified ribosomal DNA restriction enzyme analysis, pulsed-field gel electrophoresis, and ribotyping (8, 10, 12). Recently, the original Brevibacterium linens group was split into two species on the basis of their physiological and biochemical characteristics, the sugar and polyol composition of their teichoic acids, and their 16S rRNA sequence and DNA-DNA hybridization levels. One species remains B. linens and is represented by type strain ATCC 9172. The other, represented by type strain ATCC 9175, has been renamed Brevibacterium aurantiacum. Regarding this new classification, the taxonomic position of cheese-related isolates has to be revisited and potential relationships between phylogenetic affiliation and the potential occurrence of given metabolic characteristics redefined (7). The unfinished genome sequence of B. aurantiacum ATCC 9174 has recently been released by the Joint Genome Institute (http://genome.jgi-psf.org/draft_microbes/breli/breli.home.html). The development of focused phylogenetic approaches using multiple markers in conjunction with whole-genome screening techniques such as comparative genomic hybridization (CGH) has proven to be useful for the detailed characterization of pathogenic species, including food pathogens (3, 5, 9). However, only a few technological species have been investigated at an intraspecies level (2). Our intention was thus to develop modern tools to facilitate the typing of strains of technological interest, for which Brevibacteriaceae could be used as a case study. 相似文献
139.
Plasma fractionation by dead-end membrane filtration: effects of membrane properties and plasma flux
Plasma fractionation by membrane filtration permits the reinfusion of the patient with his own albumin. In this study, the influence of membrane nature and plasma flux on plasma fractionation in dead-end mode is investigated with acetate hollow fiber filters. It is found that transmembrane pressure TMP rises exponentially with time, the rate of increase being proportional to plasma flux. The faster TMP rises, the faster the drop in sieving coefficient SC. It is also found that albumin SC is a function of TMP and not of plasma flux. Theoretical analysis of the dead-end filtration was performed. This theoretical model indicates that the observed variation of TMP with time is consistent with the assumptions that pore volume decreases proportionally to the filtrate plasma volume. 相似文献
140.