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51.
Tatsuya Kunisue Jeffrey W. Fisher Babatope Fatuyi Kurunthachalam Kannan 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(21):1725-1730
Perchlorate can competitively inhibit iodide uptake by the thyroid gland (TG) via the sodium/iodide symporter, consequently reducing the production of thyroid hormones (THs). Until recently, the effects of perchlorate on TH homeostasis are being examined through measurement of serum levels of TH, by immunoassay (IA)-based methods. IA methods are fast, but for TH analysis, they are compromised by the lack of adequate specificity. Therefore, selective and sensitive methods for the analysis of THs in TG are needed, for assessment of the effects of perchlorate on TH homeostasis. In this study, we developed a method for the analysis of six THs: l-thyroxine (T4), 3,3′,5-triiodo-l-thyronine (T3), 3,3′,5′-triiodo-l-thyronine (rT3), 3,5-diiodo-l-thyronine (3,5-T2), 3,3′-diiodo-l-thyronine (3,3′-T2), and 3-iodo-l-thyronine (3-T1) in TG, using liquid chromatography (LC)–tandem mass spectrometry (MS/MS). TGs used in this study were from rats that had been placed on either iodide-deficient diet or iodide-sufficient diet, and that had either been provided with perchlorate in drinking water (10 mg/kg/day) or control water. TGs were extracted by pronase digestion and then analyzed by LC–MS/MS. The instrumental calibration range for each TH ranged from 1 to 200 ng/ml and showed a high linearity (r > 0.99). The method quantification limits (LOQs) were determined to be 0.25 ng/mg TG for 3-T1; 0.33 ng/mg TG for 3,3′- and 3,5-T2; and 0.52 ng/mg TG for rT3, T3, and T4. Rats were placed on an iodide-deficient or -sufficient diet for 2.5 months, and for the last 2 weeks of that period were provided either perchlorate (10 mg/kg/day) in drinking water or control water. Iodide deficiency and perchlorate administration both reduced TG stores of rT3, T3, and T4. In iodide-deficient rats, perchlorate exacerbated the reduction in levels of THs in TG. With the advances in analytical methodology, the use of LC–MS/MS for measurement of hormone levels in TG will allow more comprehensive evaluations of the hypothalamic-pituitary–thyroid axis. 相似文献
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54.
K. Sivakumar Maloy Kumar Sahu T. Thangaradjou L. Kannan 《Indian journal of microbiology》2007,47(3):186-196
Marine actinobacteriology is one of the major emerging areas of research in tropics. Marine actinobacteria occur on the sediments
and in water and also other biomass (mangrove) and substrates (animal). These organisms are gaining importance not only for
their taxonomic and ecological perspectives, but also for their unique metabolites and enzymes. Many earlier studies on these
organisms were confined only to the temperate regions. In tropical environment, investigations on them have gained importance
only in the last two decades. So far, from the Indian peninsula, 41 species of actinobacteria belonging to 8 genera have been
recorded. The genus, Streptomyces of marine origin has been more frequently recorded. Of 9 maritime states of India, only 4 have been extensively covered for
the study of marine actinobacteria. Most of the studies conducted pertain to isolation, identification and maintenance of
these organisms in different culture media. Further, attention has been focused on studying their antagonistic properties
against different pathogens. Their biotechnological potentials are yet to be fully explored. 相似文献
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56.
Dharmu I Ramamurty N Kannan R Babu M 《In vitro cellular & developmental biology. Animal》2007,43(8-9):306-314
The hemolymph-derived achatininH (lectin) from Achatina fulica showed a marked cytotoxic effect on MCF7, a human mammary carcinoma cell line. IC50 values as measured by the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay for achatininH ranged from 6 to 10 μg/ml in the MCF7 cells. MCF7 cells showed significant morphological changes leading to cell death. The
above cell death was observed after 48 h of treatment with 8 μg/ml when compared to untreated cells. Alterations in the tumor
marker enzymes, as well as in antioxidant enzymes, were observed after achatininH treatment. The specificity and purity of the achatininH was confirmed by the Western blot assay. AchatininH binding to MCF7 cells was detected by anti-achatininH, and visualization of the achatininH binding sites on confluent MCF7 cells was confirmed by flourescein isothiocyanate conjugated secondary antibody. MCF7-treated
cells fluoresced, indicating the presence of achatininH binding sites. Fluorescence-activated cell sorting analysis of the cell cycle showed a significant increase in S-phase in
MCF7 cells after 48 h of achatininH treatment. The cells were arrested in G2/M phase of the cell cycle after 48 h with significant changes in cell viability. Cellular damage was confirmed by agarose
gel electrophoresis with the characteristic appearance of a DNA streak in treated MCF7 cells indicating the ongoing apoptosis.
An erratum to this article can be found at 相似文献
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58.
Zhi Liu Esther C. Leng Kannan Gunasekaran Martin Pentony Min Shen Monique Howard Janelle Stoops Kathy Manchulenko Vladimir Razinkov Hua Liu William Fanslow Zhonghua Hu Nancy Sun Haruki Hasegawa Rutilio Clark Ian N. Foltz Wei Yan 《The Journal of biological chemistry》2015,290(12):7535-7562
Producing pure and well behaved bispecific antibodies (bsAbs) on a large scale for preclinical and clinical testing is a challenging task. Here, we describe a new strategy for making monovalent bispecific heterodimeric IgG antibodies in mammalian cells. We applied an electrostatic steering mechanism to engineer antibody light chain-heavy chain (LC-HC) interface residues in such a way that each LC strongly favors its cognate HC when two different HCs and two different LCs are co-expressed in the same cell to assemble a functional bispecific antibody. We produced heterodimeric IgGs from transiently and stably transfected mammalian cells. The engineered heterodimeric IgG molecules maintain the overall IgG structure with correct LC-HC pairings, bind to two different antigens with comparable affinity when compared with their parental antibodies, and retain the functionality of parental antibodies in biological assays. In addition, the bispecific heterodimeric IgG derived from anti-HER2 and anti-EGF receptor (EGFR) antibody was shown to induce a higher level of receptor internalization than the combination of two parental antibodies. Mouse xenograft BxPC-3, Panc-1, and Calu-3 human tumor models showed that the heterodimeric IgGs strongly inhibited tumor growth. The described approach can be used to generate tools from two pre-existent antibodies and explore the potential of bispecific antibodies. The asymmetrically engineered Fc variants for antibody-dependent cellular cytotoxicity enhancement could be embedded in monovalent bispecific heterodimeric IgG to make best-in-class therapeutic antibodies. 相似文献
59.
The catalytic domain of epidermal growth factor receptor (EGFR) is activated by dimerization, which requires allosteric coupling between distal dimerization and catalytic sites. Although crystal structures of EGFR kinases, solved in various conformational states, have provided important insights into EGFR activation by dimerization, the atomic details of how dimerization signals are dynamically coupled to catalytic regions of the kinase core are not fully understood. In this study, we have performed unrestrained and targeted molecular dynamics simulations on the active and inactive states of EGFR, followed by principal component analysis on the simulated trajectories, to identify correlated motions in the EGFR kinase domain upon dimerization. Our analysis reveals that the conformational changes associated with the catalytic functions of the kinase core are highly correlated with motions in the juxtamembrane (JM) and C-terminal tail, two flexible structural elements that play an active role in EGFR kinase activation and dimerization. In particular, the opening and closing of the ATP binding lobe relative to the substrate binding lobe is highly correlated with motions in the JM and C-terminal tail, suggesting that ATP and substrate binding can be coordinated with dimerization through conformational changes in the JM and C-terminal tail. Our study pinpoints key residues involved in this conformational coupling, and provides new insights into the role of the JM and C-terminal tail segments in EGFR kinase functions. 相似文献
60.
Sugar-amino acid-nucleosides (SAAN) were synthesized to mimic glycosyl nucleotide donors based on the hypothesis that a basic amino acid may interact with carboxylate groups of the enzyme in a manner similar to the diphosphate metal ion complex. C-Glycoside analogues of the d-galactopyranose or l-arabinofuranose ring systems, and four amino acids (lysine, glutamine, tryptophan, and histidine), were chosen for this study. The targets were synthesized and tested against GlfT2, a galactofuranosyltransferase essential for cell wall galactan biosynthesis in Mycobacterium tuberculosis. The inhibition assay showed that analogues containing histidine and tryptophan are moderate inhibitors of GlfT2. 相似文献