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61.
The neonatal isoform of the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 1 (SERCA1b) is a dominant Ca2+ pump in the young fibers of regenerating muscle. In vivo transfection of about 1% of the fibers with SERCA1b RNAi plasmid
resulted in no apparent change in the transfected fibers, but enhanced the increase of fresh weight and fiber size in the
whole regenerating rat soleus muscle, until the normal size was reached. Co-transfection of calcineurin inhibitor cain/cabin-1
with SERCA1b RNAi was sufficient to cut down the widespread growth stimulation, but the subsequent transfection of cain into
the SERCA1b RNAi transfected muscle did not inhibit muscle growth. The SERCA1b RNAi preferably upregulated the expression
of the NFAT reporter lacZ compared to controls when co-transfected into the fibers. Notably, perimuscular injection of interleukin-4
(IL-4) antibody but not that of an unrelevant antibody completely abolished the growth-promoting effect of SERCA1b RNAi. This
indicates that silencing SERCA1b in a few fibers stimulates the calcineurin-NFAT-IL-4 pathway and fiber growth in the whole
regenerating soleus. These results suggest the presence of an autocrine–paracrine coordination of growing muscle fibers, and
put forward a new method to stimulate skeletal muscle regeneration. 相似文献
62.
Linser R 《Journal of biomolecular NMR》2011,51(3):221-226
Proteins with excessive deuteration give access to proton detected solid-state NMR spectra of extraordinary resolution and
sensitivity. The high spectral quality achieved after partial proton back-exchange has been shown to start a new era for backbone
assignment, protein structure elucidation, characterization of protein dynamics, and access to protein parts undergoing motion.
The large absence of protons at non-exchangeable sites, however, poses a serious hurdle for characterization of side chains,
which play an important role especially for structural understanding of the protein core and the investigation of protein–protein
and protein–ligand interactions, e.g. This has caused the perdeuteration approach to almost exclusively be amenable to backbone
characterization only. In this work it is shown that a combination of isotropic 13C mixing with long-range 1H/13C magnetization transfers can be used effectively to also access complete sets of side-chain chemical shifts in perdeuterated
proteins and correlate these with the protein backbone with high unambiguity and resolution. COmbined POlarization from long-Range transfers And Direct Excitation (COPORADE) allows this strategy to yield complete sets of aliphatic amino acid resonances with reasonable sensitivity. 相似文献
63.
Lohse B Kristensen JL Kristensen LH Agger K Helin K Gajhede M Clausen RP 《Bioorganic & medicinal chemistry》2011,19(12):3625-3636
Methylated lysines are important epigenetic marks. The enzymes involved in demethylation have recently been discovered and found to be involved in cancer development and progression. Despite the relative recent discovery of these enzymes a number of inhibitors have already appeared. Most of the inhibitors are either previously reported inhibitors of related enzymes or compounds derived from these. Development in terms of selectivity and potency is still pertinent. Several reports on the development of functional assays have been published. 相似文献
64.
Nicklas H Staunstrup Nynne Sharma Rasmus O Bak Lars Svensson Thomas K Petersen Lene Aarenstrup Karsten Kristiansen Lars Bolund Jacob Giehm Mikkelsen 《BMC biotechnology》2011,11(1):33
Background
Analogues of vitamin D3 are extensively used in the treatment of various illnesses, such as osteoporosis, inflammatory skin diseases, and cancer. Functional testing of new vitamin D3 analogues and formulations for improved systemic and topical administration is supported by sensitive screening methods that allow a comparative evaluation of drug properties. As a new tool in functional screening of vitamin D3 analogues, we describe a genomically integratable sensor for sensitive drug detection. This system facilitates assessment of the pharmacokinetic and pharmadynamic properties of vitamin D3 analogues. The tri-cistronic genetic sensor encodes a drug-sensoring protein, a reporter protein expressed from an activated sensor-responsive promoter, and a resistance marker. 相似文献65.
Madsen RK Lundstedt T Gabrielsson J Sennbro CJ Alenius GM Moritz T Rantapää-Dahlqvist S Trygg J 《Arthritis research & therapy》2011,13(1):R19
Introduction
The aim of this study was to assess the feasibility of diagnosing early rheumatoid arthritis (RA) by measuring selected metabolic biomarkers. 相似文献66.
A BAC transgenic Hes1-EGFP reporter reveals novel expression domains in mouse embryos 总被引:1,自引:0,他引:1
Klinck R Füchtbauer EM Ahnfelt-Rønne J Serup P Jensen JN Jørgensen MC 《Gene expression patterns : GEP》2011,11(7):415-426
Expression of the basic helix-loop-helix factor Hairy and Enhancer of Split-1 (Hes1) is required for normal development of a number of tissues during embryonic development. Depending on context, Hes1 may act as a Notch signalling effector which promotes the undifferentiated and proliferative state of progenitor cells, but increasing evidence also points to Notch independent regulation of Hes1 expression. Here we use high resolution confocal scanning of EGFP in a novel BAC transgenic mouse reporter line, Tg(Hes1-EGFP)1Hri, to analyse Hes1 expression from embryonic day 7.0 (e7.0). Our data recapitulates some previous observations on Hes1 expression and suggests new, hitherto unrecognised expression domains including expression in the definitive endoderm at early somite stages before gut tube closure and thus preceding organogenesis. This mouse line will be a valuable tool for studies addressing the role of Hes1 in a number of different research areas including organ specification, development and regeneration. 相似文献
67.
Yan G Zhang G Fang X Zhang Y Li C Ling F Cooper DN Li Q Li Y van Gool AJ Du H Chen J Chen R Zhang P Huang Z Thompson JR Meng Y Bai Y Wang J Zhuo M Wang T Huang Y Wei L Li J Wang Z Hu H Yang P Le L Stenson PD Li B Liu X Ball EV An N Huang Q Zhang Y Fan W Zhang X Li Y Wang W Katze MG Su B Nielsen R Yang H Wang J Wang X Wang J 《Nature biotechnology》2011,29(11):1019-1023
The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus macaque. Comparison with the previously sequenced Indian rhesus macaque reveals that all three macaques maintain abundant genetic heterogeneity, including millions of single-nucleotide substitutions and many insertions, deletions and gross chromosomal rearrangements. By assessing genetic regions with reduced variability, we identify genes in each macaque species that may have experienced positive selection. Genetic divergence patterns suggest that the cynomolgus macaque genome has been shaped by introgression after hybridization with the Chinese rhesus macaque. Macaque genes display a high degree of sequence similarity with human disease gene orthologs and drug targets. However, we identify several putatively dysfunctional genetic differences between the three macaque species, which may explain functional differences between them previously observed in clinical studies. 相似文献
68.
Metabolite profiling of industrially important suspension-cultured mammalian cells is being increasingly used for rational improvement of bioprocesses. This requires the generation of global metabolite profiles that cover a broad range of metabolites and that are representative of the cells at the time of sampling. The protocol described here is a validated method for recovery of physiologically relevant amounts of key metabolites from suspension-cultured mammalian cells. The method is a two-step process consisting of initial quenching of the cells (to stop cellular metabolism and allow isolation of the cells) followed by extraction of the metabolites. The cells are quenched in 60% methanol supplemented with 0.85% (wt/vol) ammonium bicarbonate at -40 °C. Metabolites are then extracted from the quenched cells using two 100% methanol extractions followed by a single water extraction. Metabolite samples generated using this protocol are amenable to analysis by mass spectrometry-based techniques (e.g., gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry), NMR spectroscopy and enzymatic assays. 相似文献
69.
Marili Laas Kalev Adamson Irene Barnes Josef Janouek Martin S. Mullett Katarína Adam
íkov Mitsuteru Akiba Ludwig Beenken Helena Braganca Timur S. Bulgakov Paolo Capretti Thomas Cech Michelle Cleary Rasmus Enderle Luisa Ghelardini Libor Jankovský Svetlana Markovskaja Iryna Matsiakh Joana B. Meyer Funda Oskay Barbara Pikur Kristina Raitelaityt Duan Sadikovi Rein Drenkhan 《Molecular Plant Pathology》2022,23(11):1620
Lecanosticta acicola is a pine needle pathogen causing brown spot needle blight that results in premature needle shedding with considerable damage described in North America, Europe, and Asia. Microsatellite and mating type markers were used to study the population genetics, migration history, and reproduction mode of the pathogen, based on a collection of 650 isolates from 27 countries and 26 hosts across the range of L. acicola. The presence of L. acicola in Georgia was confirmed in this study. Migration analyses indicate there have been several introduction events from North America into Europe. However, some of the source populations still appear to remain unknown. The populations in Croatia and western Asia appear to originate from genetically similar populations in North America. Intercontinental movement of the pathogen was reflected in an identical haplotype occurring on two continents, in North America (Canada) and Europe (Germany). Several shared haplotypes between European populations further suggests more local pathogen movement between countries. Moreover, migration analyses indicate that the populations in northern Europe originate from more established populations in central Europe. Overall, the highest genetic diversity was observed in south‐eastern USA. In Europe, the highest diversity was observed in France, where the presence of both known pathogen lineages was recorded. Less than half of the observed populations contained mating types in equal proportions. Although there is evidence of some sexual reproduction taking place, the pathogen spreads predominantly asexually and through anthropogenic activity. 相似文献
70.