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101.
Defining the mechanisms and consequences of protein adduction is crucial to understanding the toxicity of reactive electrophiles. Application of tandem mass spectrometry and data analysis algorithms enables detection and mapping of chemical adducts at the level of amino acid sequence. Nevertheless, detection of adducts does not indicate relative reactivity of different sites. Here, we describe a method to measure the kinetics of competing adduction reactions at different sites on the same protein. Adducts are formed by electrophiles at Cys14 and Cys47 on the metabolic enzyme glutathione-S-transferase P1-1 and modification is accompanied by a loss of enzymatic activity. Relative quantitation of protein adducts was done by tagging N-termini of peptide digests with isotopically labeled phenyl isocyanate and tracking the ratio of light-tagged peptide adducts to heavy-tagged reference samples in liquid chromatography-tandem mass spectrometry analyses using a multiple reaction monitoring method. This approach was used to measure rate constants for adduction at both positions with two different model electrophiles, N-iodoacetyl-N-biotinylhexylenediamine and 1-biotinamido-4-(4'-[maleimidoethyl-cyclohexane]-carboxamido)butane. The results indicate that Cys47 was approximately two- to three-fold more reactive toward both electrophiles than was Cys14. This result was consistent with the relative reactivity of these electrophiles in a complex proteome system and with previously reported trends in reactivity of these sites. Kinetic analyses of protein modification reactions provide a means of evaluating the selectivity of reactive mediators of chemical toxicity. 相似文献
102.
The neutral exopolysaccharide produced by Lactobacillus delbrueckii ssp. bulgaricus LBB.B26 in skimmed milk was found to be composed of d-glucose and d-galactose in a molar ratio of 2:3. Linkage analysis and 1D/2D NMR ((1)H and (13)C) studies performed on the native polysaccharide, and on an oligosaccharide obtained from a partial acid hydrolysate of the native polysaccharide, showed the polysaccharide to consist of branched pentasaccharide repeating units with the following structure. [structure: see text] 相似文献
103.
Proposed minimum reporting standards for chemical analysis 总被引:4,自引:0,他引:4
Lloyd W. Sumner Alexander Amberg Dave Barrett Michael H. Beale Richard Beger Clare A. Daykin Teresa W.-M. Fan Oliver Fiehn Royston Goodacre Julian L. Griffin Thomas Hankemeier Nigel Hardy James Harnly Richard Higashi Joachim Kopka Andrew N. Lane John C. Lindon Philip Marriott Andrew W. Nicholls Michael D. Reily John J. Thaden Mark R. Viant 《Metabolomics : Official journal of the Metabolomic Society》2007,3(3):211-221
There is a general consensus that supports the need for standardized reporting of metadata or information describing large-scale
metabolomics and other functional genomics data sets. Reporting of standard metadata provides a biological and empirical context
for the data, facilitates experimental replication, and enables the re-interrogation and comparison of data by others. Accordingly,
the Metabolomics Standards Initiative is building a general consensus concerning the minimum reporting standards for metabolomics
experiments of which the Chemical Analysis Working Group (CAWG) is a member of this community effort. This article proposes
the minimum reporting standards related to the chemical analysis aspects of metabolomics experiments including: sample preparation,
experimental analysis, quality control, metabolite identification, and data pre-processing. These minimum standards currently
focus mostly upon mass spectrometry and nuclear magnetic resonance spectroscopy due to the popularity of these techniques
in metabolomics. However, additional input concerning other techniques is welcomed and can be provided via the CAWG on-line
discussion forum at or . Further, community input related to this document can also be provided via this electronic forum.
The contents of this paper do not necessarily reflect any position of the Government or the opinion of the Food and Drug Administration
Sponsor: Metabolomics Society http://www.metabolomicssociety.org/
Reference: http://msi-workgroups.sourceforge.net/bio-metadata/reporting/pbc/
http://msi-workgroups.sourceforge.net/chemical-analysis/
Version: Revision: 5.1
Date: 09 January, 2007 相似文献
104.
The ubiquitin proteasome system (UPS) represents a major pathway for intracellular protein degradation. Proteasome dependent protein quality control participates in cell cycle, immune response and apoptosis. Therefore, the UPS is in focus of therapeutic investigations and the development of pharmaceutical agents. Detailed analyses on proteasome structure and function are the foundation for drug development and clinical studies. Proteomic approaches contributed significantly to our current knowledge in proteasome research. In particular, 2-DE has been essential in facilitating the development of current models on molecular composition and assembly of proteasome complexes. Furthermore, developments in MS enabled identification of UPS proteins and their PTMs at high accuracy and high-throughput. First results on global characterization of the UPS are also available. Although the UPS has been intensively investigated within the last two decades, its functional significance and contribution to the regulation of cell and tissue phenotypes remain to be explored. This review recapitulates a variety of applied proteomic approaches in proteasome exploration, and presents an overview of current technologies and their potential in driving further investigations. 相似文献
105.
Comparative quantitative proteomics to investigate the remodeling of bioenergetic pathways under iron deficiency in Chlamydomonas reinhardtii 总被引:2,自引:0,他引:2
Naumann B Busch A Allmer J Ostendorf E Zeller M Kirchhoff H Hippler M 《Proteomics》2007,7(21):3964-3979
The basic question addressed in this study is how energy metabolism is adjusted to cope with iron deficiency in Chlamydomonas reinhardtii. To investigate the impact of iron deficiency on bioenergetic pathways, comparative proteomics was combined with spectroscopic as well as voltametric oxygen measurements to assess protein dynamics linked to functional properties of respiratory and photosynthetic machineries. Although photosynthetic electron transfer is largely compromised under iron deficiency, our quantitative and spectroscopic data revealed that the functional antenna size of photosystem II (PSII) significantly increased. Concomitantly, stress-related chloroplast polypeptides, like 2-cys peroxiredoxin and a stress-inducible light-harvesting protein, LhcSR3, as well as a novel light-harvesting protein and several proteins of unknown function were induced under iron-deprivation. Respiratory oxygen consumption did not decrease and accordingly, polypeptides of respiratory complexes, harboring numerous iron-sulfur clusters, were only slightly diminished or even increased under low iron. Consequently, iron-deprivation induces a transition from photoheterotrophic to primarily heterotrophic metabolism, indicating that a hierarchy for iron allocations within organelles of a single cell exists that is closely linked with the metabolic state of the cell. 相似文献
106.
A bioactive foam reactor (BFR), a novel bioreactor operated using surfactant foams and suspended microorganisms for the treatment
of gaseous toluene, was investigated to characterize its performance with respect to the mass transfer and biodegradation
rates. The BFR system consisted of two reactors in series; a foam column for toluene mass transfer using fine bubbles and
a cell reservoir where suspended microorganisms actively biodegraded toluene. In this study, a series of short-term experiments
demonstrated that the BFR could achieve stable removal performance and a high elimination capacity (EC) for toluene at 100.3 g/m3/h. A numerical model, combining mass balance equations for the mass transfer and subsequent biodegradation, resulted in reasonable
agreement with the experimental findings. At an inlet toluene concentration of 100 ppmv, the toluene concentration in the liquid phase remained extremely low, indicating that the microbial activity was not hindered
in the BFR system. However, the experimental and model prediction results showed that the actual mass of toluene transferred
into the liquid phase was not closely balanced with the amount of toluene biodegraded in the BFR used in this study. Consequently,
methods, such as increasing the effective volume of the foam column or the mass transfer coefficient, need to be implemented
to achieve higher toluene EC and better BFR performance. 相似文献
107.
Fibroblast growth factor receptors (FGFRs) are a family of four transmembrane (TM) receptor tyrosine kinases (RTKs) which bind to a large family of fibroblast growth factor (FGF) ligands with varying affinity and specificity. FGFR signaling regulates many physiological and pathological processes in development and tissue homeostasis. Understanding FGFR signaling processes requires the identification of partner proteins which regulate receptor function and biological outputs. In this study, we employ an epitope-tagged, covalently dimerized, and constitutively activated form of FGFR1 to identify potential protein partners by MS. By this approach, we sample candidate FGFR effectors throughout the life history of the receptor. Functional classification of the partners identified revealed specific subclasses involved in protein biosynthesis and folding; structural and regulatory components of the cytoskeleton; known signaling effectors and small GTPases implicated in endocytosis and vesicular trafficking. The kinase dependency of the interaction was determined for a subset of previously unrecognized partners by coimmunoprecipitation, Western blotting, and immunocytochemistry. From this group, the small GTPase Rab5 was selected for functional interrogation. We show that short hairpin (sh) RNA-mediated depletion of Rab5 attenuates the activation of the extracellular-regulated kinase (ERK) 1/2 pathway by FGFR signaling. The strategic approach adopted in this study has revealed bona fide novel effectors of the FGFR signaling pathway. 相似文献
108.
Draisci R Montesissa C Santamaria B D'Ambrosio C Ferretti G Merlanti R Ferranti C De Liguoro M Cartoni C Pistarino E Ferrara L Tiso M Scaloni A Cosulich ME 《Proteomics》2007,7(17):3184-3193
Surveillance of illegal use of steroids hormones in cattle breeding is a key issue to preserve human health. To this purpose, an integrated approach has been developed for the analysis of plasma and urine from calves treated orally with a single dose of a combination of the androgenic steroids boldenone and boldione. A quantitative estimation of steroid hormones was obtained by LC-APCI-Q-MS/MS analysis of plasma and urine samples obtained at various times up to 36 and 24 h after treatment, respectively. These experiments demonstrated that boldione was never found, while boldenone alpha- and beta-epimers were detected in plasma and urine only within 2 and 24 h after drug administration, respectively. Parallel proteomic analysis of plasma samples was obtained by combined 2-DE, MALDI-TOF-MS and muLC-ESI-IT-MS/MS procedures. A specific protein, poorly represented in normal plasma samples collected before treatment, was found upregulated even 36 h after hormone treatment. Extensive mass mapping experiments proved this component as an N-terminal truncated form of apolipoprotein A1 (ApoA1), a protein involved in cholesterol transport. The expression profile of ApoA1 analysed by Western blot analysis confirmed a significant and time dependent increase of this ApoA1 fragment. Then, provided that further experiments performed with a growth-promoting schedule will confirm these preliminary findings, truncated ApoA1 may be proposed as a candidate biomarker for steroid boldenone and possibly other anabolic androgens misuse in cattle veal calves, when no traces of hormones are detectable in plasma or urine. 相似文献
109.
This paper studies the impact on reported coronavirus 2019 (COVID-19) cases and deaths in Spain resulting from large mass gatherings that occurred from March 6 to March 8, 2020. To study these outcomes, the geographic differences in the planned pre-pandemic major events that took place on these dates were exploited, which is a quasi-random source of variation for identification purposes. We collected daily and detailed information about the number of attendees at football (soccer) and basketball matches in addition to individuals participating in the Women’s Day marches across Spain, which we merged with daily data on reported COVID-19 cases and deaths at the provincial level. Our results reveal evidence of non-negligible COVID-19 cases related to the differences in the percentage of attendees at these major events from March 6 to March 8. In a typical province, approximately 31% of the average daily reported COVID-19 cases per 100,000 inhabitants between mid-March and early April 2020 can be explained by the participation rate in those major events. A back-of-the-envelope calculation suggests that this implies almost five million euros (169,000 euros/day) of additional economic cost in the health system of a typical province with one million inhabitants in the period under consideration. Several mechanisms behind the spread of COVID-19 are also examined. 相似文献
110.
We review recent advances in our ability to characterise biomolecular structure, interactions and associated dynamics by mass photometry (MP), the label-free detection and mass measurement of individual biomolecules in solution. Molecular counting and identification provides direct access to relative abundance, and thereby affinities, while associated dynamics yield on- and off-rates. The molecular resolution afforded by MP enables these measurements as a function of stoichiometry and assembly at equilibrium, as opposed to the majority of existing solution-based methods. Together with future improvements in terms of assays and technological performance, MP is likely to provide mechanistic details of complex biomolecular processes. 相似文献