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51.
Song JK Kannan R Merdes G Singh J Mlodzik M Giniger E 《Development (Cambridge, England)》2010,137(21):3719-3727
Abl is an essential regulator of cell migration and morphogenesis in both vertebrates and invertebrates. It has long been speculated that the adaptor protein Disabled (Dab), which is a key regulator of neuronal migration in the vertebrate brain, might be a component of this signaling pathway, but this idea has been controversial. We now demonstrate that null mutations of Drosophila Dab result in phenotypes that mimic Abl mutant phenotypes, both in axon guidance and epithelial morphogenesis. The Dab mutant interacts genetically with mutations in Abl, and with mutations in the Abl accessory factors trio and enabled (ena). Genetic epistasis tests show that Dab functions upstream of Abl and ena, and, consistent with this, we show that Dab is required for the subcellular localization of these two proteins. We therefore infer that Dab is a bona fide component of the core Abl signaling pathway in Drosophila. 相似文献
52.
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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55.
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
56.
Subramanya SB Rajendran VM Srinivasan P Nanda Kumar NS Ramakrishna BS Binder HJ 《American journal of physiology. Gastrointestinal and liver physiology》2007,293(4):G857-G863
Electroneutral Na absorption occurs in the intestine via sodium-hydrogen exchanger (NHE) isoforms NHE2 and NHE3. Bicarbonate and butyrate both stimulate electroneutral Na absorption through NHE. Bicarbonate- but not butyrate-dependent Na absorption is inhibited by cholera toxin (CT). Long-term exposure to butyrate also influences expression of apical membrane proteins in epithelial cells. These studies investigated the effects of short- and long-term in vivo exposure to butyrate on apical membrane NHE and mRNA, protein expression, and activity in rat ileal epithelium that had been exposed to CT. Ileal loops were exposed to CT in vivo for 5 h and apical membrane vesicles were isolated. 22Na uptake was measured by using the inhibitor HOE694 to identify NHE2 and NHE3 activity, and Western blot analyses were performed. CT reduced total NHE activity by 70% in apical membrane vesicles with inhibition of both NHE2 and NHE3. Reduced NHE3 activity and protein expression remained low following removal of CT but increased to control values following incubation of the ileal loop with butyrate for 2 h. In parallel there was a 40% decrease in CT-induced increase in cAMP content. In contrast, NHE2 activity partially increased following removal of CT and was further increased to control levels by butyrate. NHE2 protein expression did not parallel its activity. Neither NHE2 nor NHE3 mRNA content were affected by CT or butyrate. These results indicate that CT has varying effects on the two apical NHE isoforms, inhibiting NHE2 activity without altering its protein expression and reducing both NHE3 activity and protein expression. Butyrate restores both CT-inhibited NHE2 and NHE3 activities to normal levels but via different mechanisms. 相似文献
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58.
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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60.
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