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201.
Ernst JM Helmreich 《Cell communication and signaling : CCS》2010,8(1):1-15
As one of the disciplines of systems biology, proteomics is central to enabling the elucidation of protein function within the cell; furthermore, the question of how to deduce protein structure and function from the genetic readout has gained new significance. This problem is of particular relevance for proteins engaged in cell signalling. In dealing with this question, I shall critically comment on the reliability and predictability of transmission and translation of the genetic blue print into the phenotype, the protein. Based on this information, I will then evaluate the intentions and goals of today's proteomics and gene-networking and appraise their chances of success. Some of the themes commented on in this publication are explored in greater detail with particular emphasis on the historical roots of concepts and techniques in my forthcoming book, published in German: Von Molekülen zu Zellen. 100 Jahre experimentelle Biologie. Betrachtungen eines Biochemikers. 相似文献
202.
203.
Roel GW Verhaak Frank JT Staal Peter JM Valk Bob Lowenberg Marcel JT Reinders Dick de Ridder 《BMC bioinformatics》2006,7(1):105-15
Background
Intensity values measured by Affymetrix microarrays have to be both normalized, to be able to compare different microarrays by removing non-biological variation, and summarized, generating the final probe set expression values. Various pre-processing techniques, such as dChip, GCRMA, RMA and MAS have been developed for this purpose. This study assesses the effect of applying different pre-processing methods on the results of analyses of large Affymetrix datasets. By focusing on practical applications of microarray-based research, this study provides insight into the relevance of pre-processing procedures to biology-oriented researchers. 相似文献204.
Background
Application of phenetic methods to gene expression analysis proved to be a successful approach. Visualizing the results in a 3-dimentional space may further enhance these techniques. 相似文献205.
Davide?Baú Alberto?JM?Martin Catherine?Mooney Alessandro?Vullo Ian?Walsh Gianluca?PollastriEmail author 《BMC bioinformatics》2006,7(1):402
Background
We describe Distill, a suite of servers for the prediction of protein structural features: secondary structure; relative solvent accessibility; contact density; backbone structural motifs; residue contact maps at 6, 8 and 12 Angstrom; coarse protein topology. The servers are based on large-scale ensembles of recursive neural networks and trained on large, up-to-date, non-redundant subsets of the Protein Data Bank. Together with structural feature predictions, Distill includes a server for prediction of C α traces for short proteins (up to 200 amino acids). 相似文献206.
Zirconyl hematoxylin stains acidic mucins darkly and specifically using a solution of 100 mg hematoxylin, 5 ml ethanol, 5 ml 0.5% sodium iodate, 400 mg zirconyl chloride octahydrate, and 30 ml 25% aqueous glycerol. The stain is especially advantageous for studying goblet cells and Paget cells. 相似文献
207.
208.
Marco van der Toorn Dirk-Jan Slebos Harold G de Bruin Renee Gras Delaram Rezayat Lucie Jorge Koen Sandra Antoon JM van Oosterhout 《Respiratory research》2013,14(1):45
Background
Cigarette smoking (CS) is the most important risk factor for COPD, which is associated with neutrophilic airway inflammation. We hypothesize, that highly reactive aldehydes are critical for CS-induced neutrophilic airway inflammation.Methods
BALB/c mice were exposed to CS, water filtered CS (WF-CS) or air for 5 days. Levels of total particulate matter (TPM) and aldehydes in CS and WF-CS were measured. Six hours after the last exposure, inflammatory cells and cytokine levels were measured in lung tissue and bronchoalveolar lavage fluid (BALF). Furthermore, Beas-2b bronchial epithelial cells were exposed to CS extract (CSE) or WF-CS extract (WF-CSE) in the absence or presence of the aldehyde acrolein and IL-8 production was measured after 24 hrs.Results
Compared to CS, in WF-CS strongly decreased (CS; 271.1 ± 41.5 μM, WF-CS; 58.5 ± 8.2 μM) levels of aldehydes were present whereas levels of TPM were only slightly reduced (CS; 20.78 ± 0.59 mg, WF-CS; 16.38 ± 0.36 mg). The numbers of mononuclear cells in BALF (p<0.01) and lung tissue (p<0.01) were significantly increased in the CS- and WF-CS-exposed mice compared to air control mice. Interestingly, the numbers of neutrophils (p<0.001) in BALF and neutrophils and eosinophils (p<0.05) in lung tissue were significantly increased in the CS-exposed but not in WF-CS-exposed mice as compared to air control mice. Levels of the neutrophil and eosinophil chemoattractants KC, MCP-1, MIP-1α and IL-5 were all significantly increased in lung tissue from CS-exposed mice compared to both WF-CS-exposed and air control mice. Interestingly, depletion of aldehydes in WF-CS extract significantly reduced IL-8 production in Beas-2b as compared to CSE, which could be restored by the aldehyde acrolein.Conclusion
Aldehydes present in CS play a critical role in inflammatory cytokine production and neutrophilic- but not mononuclear airway inflammation. 相似文献209.
Citrullination and the immune response to citrullinated proteins have been
fundamental for the early recognition of rheumatoid arthritis by serological tests
and a better understanding of its pathophysiology. In the first years after the
initial publications, the focus was on the antibodies directed to citrullinated
proteins. It is now realized that citrullinating enzymes and citrullinated proteins
may have important roles in the maintenance of the inflammatory processes in the
joints. There is also accumulating evidence for a direct role of citrullination in
tissue destruction in the rheumatoid synovium. Here we will discuss the development
and importance of anti-citrullinated protein antibodies in rheumatoid arthritis as
well as recent findings implicating citrullination in the pathophysiology of
rheumatoid arthritis.The first indication that patients with rheumatoid arthritis (RA) produce antibodies to
a specific autoantigen was published in 1964 by two Dutch scientists, Nienhuis and
Mandema. The exact nature of this antigen, the so-called perinuclear factor, remained
unclear for decades. In 1978, the target of seemingly unrelated RA-specific
autoantibodies (that is, keratin) was identified. Almost 15 years later, Guy
Serre’s group convincingly showed that both antigens were identical to the
cytokeratin filament-aggregating protein filaggrin (reviewed in [1]). Our own previously published results had shown that the newly made
precursor of filaggrin in cultured buccal mucosa cells (that is, profilaggrin) did not
react with RA antibodies [2]. This prompted us to consider the possibility that a post-translational
modification of filaggrin, absent on newly made profilaggrin, was required for the
formation of the antigenic target of these antibodies. Since 1994, we have tested
several likely modifications using synthetic peptides. Indeed, citrullination, the
enzymatic conversion of peptidylarginine into peptidylcitrulline, turned out to be
essential to make peptides reactive with RA autoantibodies. We subsequently developed an
enzyme-linked immunosorbent assay with citrullinated peptides and confirmed that the
anti-peptidylcitrulline activity was specific for RA [3]. Our further work was directed to the development of the CCP2 test, using
cyclic citrullinated peptides (CCPs) selected from random peptide libraries [4].The discovery of CCP/protein as the most prominent RA-specific antigen had great impact
on RA diagnostics and our understanding of RA pathophysiology. The following milestones
can be noted (see [5] also).1. After decades of intensive research by many groups, a specific diagnostic
test for RA had finally been developed. The CCP2 test has a specificity of more than
95%, is very sensitive (~75%), and is still considered the gold standard in RA
autoantibody testing. Since 2010, anti-citrullinated protein antibodies (ACPAs) have
been included in the new American College of Rheumatology/European League Against
Rheumatism classification criteria for RA.2. Recently, an international reference preparation for ACPAs was evaluated
by the International Committee for the Standardization of Autoantibodies in Rheumatic
and Related Diseases [6]. It is available for the scientific community via the Centers for Disease
Control and Prevention (Atlanta, GA, USA).3. A positive CCP2 test predicts the development of RA, often years before
clinical confirmation (reviewed in [5]). It appears that time to RA diagnosis is shorter in patients with high
anti-CCP2 titers at enrollment as compared with those with low titers [7].4. ACPA-positive RA is characterized by a more severe disease course. Early
treatment of ACPA-positive individuals appears to be very effective.5. ACPA-negative patients (about 25% of the total RA population) generally
display a much milder course of disease. About 35% of such ACPA-negative patients
produce anti-carbamylated protein antibodies. Interestingly, the chemical product of
carbamylation (that is, lysine converted to homocitrulline) is structurally very similar
to citrulline [8].6. Specific human leukocyte antigen (HLA) genes (DRB1 shared epitope (SE)
alleles) not only are the most important genetic risk factor for RA but also are
strongly associated with the production of ACPAs.7. The best known environmental risk factor for RA, cigarette smoking, is a
risk factor only for ACPA-positive and not for ACPA-negative RA [9]. There is increasing evidence that smoking acts as a trigger for
anti-citrulline immunity and does so mainly in the context of certain HLA genes and
certain other genetic risk factors.8. ACPAs and citrullinated antigens form immune complexes which stimulate the
inflammatory process. Continuous production of such immune complexes ultimately results
in the chronic inflammation, characteristic for RA (Figure 1).Open in a separate windowFigure 1Citrullination-related immunity and pathophysiology in rheumatoid
arthritis. In genetically susceptible individuals, an environmental factor
may initiate a primary inflammation, which can occur in various tissues, and
trigger the immune response to citrullinated proteins (left). The resulting
anti-citrullinated protein/peptide antibodies (ACPAs) are distributed through the
circulation and may form immune complexes with citrullinated proteins produced in
an inflamed synovium, thereby boosting the inflammatory process. This will be
associated with the infiltration and activation of neutrophils, macrophages, and
lymphocytes; cell death; extracellular DNA trap formation; the activation and
release of peptidylarginine deiminases (PADs); de novo citrullination;
and diversification of the ACPA response. Besides the common
inflammation-associated mediators of tissue destruction (not shown), ACPAs and
PADs can be directly involved in these processes. HLA, human leukocyte
antigen. 相似文献
210.
Rohola Hosseini Gerda EM Lamers Zlatan Hodzic Annemarie H Meijer Marcel JM Schaaf Herman P Spaink 《Autophagy》2014,10(10):1844-1857
High-resolution imaging of autophagy has been used intensively in cell culture studies, but so far it has been difficult to visualize this process in detail in whole animal models. In this study we present a versatile method for high-resolution imaging of microbial infection in zebrafish larvae by injecting pathogens into the tail fin. This allows visualization of autophagic compartments by light and electron microscopy, which makes it possible to correlate images acquired by the 2 techniques. Using this method we have studied the autophagy response against Mycobacterium marinum infection. We show that mycobacteria during the progress of infection are frequently associated with GFP-Lc3-positive vesicles, and that 2 types of GFP-Lc3-positive vesicles were observed. The majority of these vesicles were approximately 1 μm in size and in close vicinity of bacteria, and a smaller number of GFP-Lc3-positive vesicles was larger in size and were observed to contain bacteria. Quantitative data showed that these larger vesicles occurred significantly more in leukocytes than in other cell types, and that approximately 70% of these vesicles were positive for a lysosomal marker. Using electron microscopy, it was found that approximately 5% of intracellular bacteria were present in autophagic vacuoles and that the remaining intracellular bacteria were present in phagosomes, lysosomes, free inside the cytoplasm or occurred as large aggregates. Based on correlation of light and electron microscopy images, it was shown that GFP-Lc3-positive vesicles displayed autophagic morphology. This study provides a new approach for injection of pathogens into the tail fin, which allows combined light and electron microscopy imaging in vivo and opens new research directions for studying autophagy process related to infectious diseases. 相似文献