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981.
Ray R Choi M Zhang Z Silverman GA Askew D Mukherjee AB 《The Journal of biological chemistry》2005,280(11):9761-9764
Uteroglobin (UG), the founding member of the Secretoglobin superfamily, is a potent anti-inflammatory protein constitutively expressed at a high level in the airway epithelia of all mammals. We previously reported that the lungs of UG-knock-out (UG-KO) mice express elevated levels of Th2 cytokines (e.g. interleukin (IL)-4 and IL-13), which are augmented by allergen sensitization and challenge leading to exaggerated airway inflammation. Notably, these responses are suppressed by recombinant UG treatment (Mandal, A. K., Zhang, Z., Ray, R., Choi, M. S., Chowdhury, B., Pattabiraman, N., and Mukherjee, A. B. (2004) J. Exp. Med. 199, 1317-1330). Recent reports indicate that human orthologs of murine squamous cell carcinoma antigen-2 (SCCA-2/serpinb3a), a serine protease-inhibitor, are overexpressed in the airways of asthmatic patients. We report here that compared with wild type littermates, UG-KO mouse lungs express markedly elevated levels of SCCA-2 mRNA and protein, which are augmented by allergen-challenge. Most importantly, these effects are abrogated by recombinant UG treatment. We further demonstrate that treatment of cultured human bronchial epithelial cells with IL-4 or IL-13 stimulates phosphorylation of STAT-1 and STAT-6 leading to SCCA-1 (SERPINB3) and SCCA-2 (SERPINB4) gene expression. We propose that: (i) IL-4- and IL-13-stimulated SCCA gene expression is mediated via STAT-1 and STAT-6 activation, and (ii) by suppressing the production, and most likely by interfering with the signaling of these cytokines, UG inhibits SCCA gene expression associated with airway inflammation in asthma. 相似文献
982.
Hess ST Kumar M Verma A Farrington J Kenworthy A Zimmerberg J 《The Journal of cell biology》2005,169(6):965-976
Although lipid-dependent protein clustering in biomembranes mediates numerous functions, there is little consensus among membrane models on cluster organization or size. Here, we use influenza viral envelope protein hemagglutinin (HA(0)) to test the hypothesis that clustering results from proteins partitioning into preexisting, fluid-ordered "raft" domains, wherein they have a random distribution. Japan HA(0) expressed in fibroblasts was visualized by electron microscopy using immunogold labeling and probed by fluorescence resonance energy transfer (FRET). Labeled HA coincided with electron-dense, often noncircular membrane patches. Poisson and K-test (Ripley, B.D. 1977. J. R. Stat. Soc. Ser. B. 39:172-212) analyses reveal clustering on accessible length scales (20-900 nm). Membrane treatments with methyl-beta-cyclodextrin and glycosphingolipid synthesis inhibitors did not abolish clusters but did alter their pattern, especially at the shortest lengths, as was corroborated by changes in FRET efficiency. The magnitude and density dependence of the measured FRET efficiency also indicated a nonrandom distribution on molecular length scales (approximately 6-7 nm). This work rules out the tested hypothesis for HA over the accessible length scales, yet shows clearly how the spatial distribution of HA depends on lipid composition. 相似文献
983.
Vasudevan A Verzal MK Wodka D Souers AJ Blackburn C Che JL Lai S Brodjian S Falls DH Dayton BD Govek E Daniels T Geddes B Marsh KC Hernandez LE Collins CA Kym PR 《Bioorganic & medicinal chemistry letters》2005,15(14):3412-3416
The identification of a novel series of benzamide-containing MCHr1 antagonists is described. Compound 22 displayed moderate efficacy in a diet induced obesity mice model. 相似文献
984.
985.
Characterization of proteins in human pancreatic cancer serum using differential gel electrophoresis and tandem mass spectrometry 总被引:5,自引:0,他引:5
The purpose of this study was to develop techniques for identifying cancer biomarkers in human serum using differential in-gel electrophoresis (DIGE), and characterizing the protein biomarkers using tandem mass spectrometry (MS/MS). A major problem in profiling protein expression by DIGE comes from the presence of high concentrations of a small number of proteins. Therefore, serum samples were first chromatographed using an immunoaffinity HPLC column (Agilent Technologies), to selectively remove albumin, immunoglobulins, transferrin, haptoglobin, and antitrypsin. Serum samples from three individuals with pancreatic cancer and three individuals without cancer were compared. Serum samples were processed using the immunoaffinity column. Differential protein analysis was performed using DIGE. A total of 56 protein spot-features were found to be significantly increased and 43 significantly decreased in cancer serum samples. These spot features were excised, trypsin digested, and analyzed by MALDI/TOF/TOF (4700 Proteomics Analyzer, Applied Biosystems). We identified 24 unique proteins that were increased and 17 unique proteins that were decreased in cancer serum samples. Western blot analysis confirmed increased levels of several of these proteins in the pancreatic cancer serum samples. In an independent series of serum samples from 20 patients with pancreatic cancer and 14 controls, increased levels of apolipoprotein E, alpha-1-antichymotrypsin, and inter-alpha-trypsin inhibitor were found to be associated with pancreatic cancer. These results suggest that affinity column enrichment and 2-D DIGE can be used to identify numerous proteins differentially expressed in serum from individuals with pancreatic cancer. 相似文献
986.
Patwardhan AJ Strittmatter EF Camp DG Smith RD Pallavicini MG 《Journal of proteome research》2005,4(6):1952-1960
Normal and cancer cell line proteomes were profiled using high throughput mass spectrometry techniques. Application of protein-level and peptide-level sample fractionation combined with LC-MS/MS analysis enabled identification of 2235 unmodified proteins representing a broad range of functional and compartmental classes. An iterative multistep search strategy was used to identify post-translational modifications, revealing several proteins that are preferentially modified in cancer cells. Information regarding both unmodified and modified protein forms was combined with publicly available gene expression and protein-protein interaction data. The resulting integrated dataset revealed several functionally related proteins that are differentially regulated between normal and cancer cell lines. 相似文献
987.
Gajanan Sathe Chan Hyun Na Santosh Renuse Anil Madugundu Marilyn Albert Abhay Moghekar Akhilesh Pandey 《Clinical proteomics》2018,15(1):29
Background
Cerebrospinal fluid (CSF) is an important source of potential biomarkers that affect the brain. Biomarkers for neurodegenerative disorders are needed to assist in diagnosis, monitoring disease progression and evaluating efficacy of therapies. Recent studies have demonstrated the involvement of tyrosine kinases in neuronal cell death. Thus, neurodegeneration in the brain is related to altered tyrosine phosphorylation of proteins in the brain and identification of abnormally phosphorylated tyrosine peptides in CSF has the potential to ascertain candidate biomarkers for neurodegenerative disorders.Methods
In this study, we used an antibody-based tyrosine phosphopeptide enrichment method coupled with high resolution Orbitrap Fusion Tribrid Lumos Fourier transform mass spectrometer to catalog tyrosine phosphorylated peptides from cerebrospinal fluid. The subset of identified tyrosine phosphorylated peptides was also validated using parallel reaction monitoring (PRM)-based targeted approach.Results
To date, there are no published studies on global profiling of phosphotyrosine modifications of CSF proteins. We carried out phosphotyrosine profiling of CSF using an anti-phosphotyrosine antibody-based enrichment and analysis using high resolution Orbitrap Fusion Lumos mass spectrometer. We identified 111 phosphotyrosine peptides mapping to 66 proteins, which included 24 proteins which have not been identified in CSF previously. We then validated a set of 5 tyrosine phosphorylated peptides in an independent set of CSF samples from cognitively normal subjects, using a PRM-based targeted approach.Conclusions
The findings from this deep phosphotyrosine profiling of CSF samples have the potential to identify novel disease-related phosphotyrosine-containing peptides in CSF.988.
Susan Maria Gaurav Barnwal Anil Kumar Karthika Mohan Vivek Vinod Aswathi Varghese Raja Biswas 《Revista iberoamericana de micología》2018,35(3):147-150
Background
Candida parapsilosis is recognized as a species complex: Candida parapsilosis sensu stricto, Candida orthopsilosis and Candida metapsilosis are three distinct but closely related species.Aims
To determine the species and antifungal susceptibility of members of the C. parapsilosis complex, isolated from clinical samples.Methods
Isolates identified as C. parapsilosis complex by VITEK® 2 system were included. Antifungal susceptibility test was done using the VITEK® 2 semi-automated system. The distribution of the species in the complex was determined by multiplex PCR.Results
Among the seventy-seven C. parapsilosis complex isolates, C. parapsilosis sensu stricto (57.1%) was the commonest species, followed by C. orthopsilosis (40.2%) and C. metapsilosis (2.5%). All three species were susceptible to amphotericin B, caspofungin and micafungin. Among C. parapsilosis sensu stricto isolates, 16% were resistant to fluconazole while 2.2% showed dose dependent susceptibility. Also, 18.2% of C. parapsilosis sensu stricto isolates showed dose dependent susceptibility to voriconazole.Conclusions
C. parapsilosis sensu stricto was the most commonly isolated member of the C. parapsilosis complex and it showed high resistance to fluconazole. A high prevalence of C. orthopsilosis (40.2%) was also noted. 相似文献989.