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61.
62.
Ferhat Alkan Oscar G Wilkins Santiago Hernndez-Prez Sofia Ramalho Joana Silva Jernej Ule William
J Faller 《Nucleic acids research》2022,50(16):e95
Recent studies have revealed multiple mechanisms that can lead to heterogeneity in ribosomal composition. This heterogeneity can lead to preferential translation of specific panels of mRNAs, and is defined in large part by the ribosomal protein (RP) content, amongst other things. However, it is currently unknown to what extent ribosomal composition is heterogeneous across tissues, which is compounded by a lack of tools available to study it. Here we present dripARF, a method for detecting differential RP incorporation into the ribosome using Ribosome Profiling (Ribo-seq) data. We combine the ‘waste’ rRNA fragment data generated in Ribo-seq with the known 3D structure of the human ribosome to predict differences in the composition of ribosomes in the material being studied. We have validated this approach using publicly available data, and have revealed a potential role for eS25/RPS25 in development. Our results indicate that ribosome heterogeneity can be detected in Ribo-seq data, providing a new method to study this phenomenon. Furthermore, with dripARF, previously published Ribo-seq data provides a wealth of new information, allowing the identification of RPs of interest in many disease and normal contexts. dripARF is available as part of the ARF R package and can be accessed through https://github.com/fallerlab/ARF. 相似文献
63.
64.
Teng YK Verburg RJ Verpoort KN Diepenhorst GM Bajema IM van Tol MJ Jol-van der Zijde EC Toes RE Huizinga TW van Laar JM 《Arthritis research & therapy》2007,9(5):R106
In order to identify pathogenic correlates of refractory rheumatoid arthritis (RA), antibodies against anti-cyclic citrullinated
protein (ACPAs) were investigated in RA patients in whom the dysregulated immune system had been ablated by high-dose chemotherapy
(HDC) and autologous haematopoietic stem cell transplantation (HSCT). Six patients with refractory RA were extensively characterized
in terms of levels of total immunoglobulins, RA-specific autoantibodies (ACPAs and rheumatoid factor) and antibodies against
rubella, tetanus toxoid (TT) and phosphorylcholine before and after HDC plus HSCT. Additionally, the avidity of ACPAs was
measured before and after treatment and compared with the avidity of TT antibodies following repeated immunizations. Synovial
biopsies were obtained by arthroscopy before HDC plus HSCT, and analyzed by immunohistochemistry. In the three patients with
clinically long-lasting responses to HDC plus HSCT (median 423 days), significant reductions in ACPA-IgG levels after therapy
were observed (median level dropped from 215 to 34 arbitrary units/ml; P = 0.05). In contrast, stable ACPA-IgG levels were observed in three patients who relapsed shortly after HDC plus HSCT (median
of 67 days). Clinical responders had ACPA-IgG of lower avidity (r = 0.75; P = 0.08) and higher degree of inflammation histologically (r = 0.73; P = 0.09). Relapse (after 38 to 530 days) in all patients was preceded by rising levels of low avidity ACPA-IgG (after 30 to
388 days), in contrast to the stable titres of high avidity TT antibodies. In conclusion, humoral autoimmune responses were
differentially modulated by immunoablative therapy in patients with synovial inflammation and low avidity ACPA-IgG autoantibodies
as compared with patients with high levels of high avidity ACPA-IgG. The distinct clinical disease course after immunoablative
therapy based on levels and avidity of ACPA-IgG indicates that refractory RA is not a single disease entity. 相似文献
65.
Exophilin8 transiently clusters insulin granules at the actin-rich cell cortex prior to exocytosis 总被引:1,自引:0,他引:1
Exophilin8/MyRIP/Slac2-c is an effector protein of the small GTPase Rab27a and is specifically localized on retinal melanosomes and secretory granules. We investigated the role of exophilin8 in insulin granule trafficking. Exogenous expression of exophilin8 in pancreatic β cells or their cell line, MIN6, polarized (exophilin8-positive) insulin granules at the cell corners, where both cortical actin and the microtubule plus-end-binding protein, EB1, were present. Mutation analyses indicated that the ability of exophilin8 to act as a linker between Rab27a and myosin Va is essential for its granule-clustering activity. Moreover, exophilin8 and exophilin8-associated insulin granules were markedly stable and immobile. Total internal reflection fluorescence microscopy indicated that exophilin8 restricts the motion of insulin granules at a region deeper than that where another Rab27a effector, granuphilin, accumulates docked granules directly attached to the plasma membrane. However, the exophilin8-induced immobility of insulin granules was eliminated upon secretagogue stimulation and did not inhibit evoked exocytosis. Furthermore, exophilin8 depletion prevents insulin granules from being transported close to the plasma membrane and inhibits their fusion. These findings indicate that exophilin8 transiently traps insulin granules into the cortical actin network close to the microtubule plus-ends and supplies them for release during the stimulation. 相似文献
66.
Joana D. Amaral Ricardo J. S. Viana Rita M. Ramalho Clifford J. Steer Cec��lia M. P. Rodrigues 《Journal of lipid research》2009,50(9):1721-1734
Bile acids are a group of molecular species of acidic steroids with peculiar physical-chemical and biological characteristics. At high concentrations they become toxic to mammalian cells, and their presence is pertinent in the pathogenesis of several liver diseases and colon cancer. Bile acid cytoxicity has been related to membrane damage, but also to nondetergent effects, such as oxidative stress and apoptosis. Strikingly, hydrophilic ursodeoxycholic acid (UDCA), and its taurine-conjugated form (TUDCA), show profound cytoprotective properties. Indeed, these molecules have been described as potent inhibitors of classic pathways of apoptosis, although their precise mode of action remains to be clarified. UDCA, originally used for cholesterol gallstone dissolution, is currently considered the first choice therapy for several forms of cholestatic syndromes. However, the beneficial effects of both UDCA and TUDCA have been tested in other experimental pathological conditions with deregulated levels of apoptosis, including neurological disorders, such as Alzheimer''s, Parkinson''s, and Huntington''s diseases. Here, we review the role of bile acids in modulating the apoptosis process, emphasizing the anti-apoptotic effects of UDCA and TUDCA, as well as their potential use as novel and alternate therapeutic agents for the treatment of apoptosis-related diseases. 相似文献
67.
Pizetta Carolina Senhorinho Ramalho Ribeiro William Rafael Ferreira Amanda Lopes da Costa Moura Matheus Bonfim Kenny Pinheiro Patrícia Valle Cabral Glaucia Barbosa Aragão Francisco José Lima 《Plant Cell, Tissue and Organ Culture》2022,148(2):281-291
Plant Cell, Tissue and Organ Culture (PCTOC) - Whitefly (Bemisia tabaci) is a polyphagous insect that causes huge damage in several horticultural crops, including tomato, by sucking nutrients from... 相似文献
68.
Comparison of resistance to drought of three bean cultivars 总被引:4,自引:0,他引:4
The aim of the present work was to evaluate oxidative stress and plant antioxidant system of three contrasting bean (Phaseolus vulgaris L.) genotypes in the response to drought. Drought was imposed 14 d after emergence, by withholding water, until leaf relative
water content reached 65 %. Water stress increased lipid peroxidation (LPO), membrane injury index, H2O2 and OH⋅ production in leaves of stressed plants. Activities of the antioxidative enzymes superoxide dismutase (SOD) and ascorbate
peroxidase (APOX) increased significantly under water stress in all the studied cultivars, while catalase (CAT) increased
in cvs. Plovdiv 10 and Prelom, but decreased in cv. Dobrudjanski ran. Furthermore cv. Plovdiv 10 which had the highest APOX
and CAT activities also showed the lowest increase in H2O2 and OH⋅ production and LPO while cv. Dobrudjanski ran showed the lowest increases (and often the lowest values) in the antioxidant
enzyme activities and the highest increases of H2O2 and OH⋅ production, and LPO. On the basis of the data obtained we could specify cv. Plovdiv 10 and cv. Prelom as drought tolerant
and cv. Dobrudjanski ran as a drought sensitive. 相似文献
69.
Araújo CP Gurgel CA Ramos EA Freitas VS Barbosa Ade A Ramalho LM dos Santos JN 《Journal of molecular histology》2010,41(6):357-365
LCs and MCs are known to be directly influenced by UV radiation. This study investigated the presence of Langerhans cells
(LCs) and mast cells (MCs) in actinic cheilitis (AC) exhibiting epithelial dysplasia (ED). Using immunohistochemistry for
CD1a and mast cell tryptase, LCs and MCs density was assessed in 35 cases of AC with different degrees of ED. LCs were found
in 32 cases of AC whereas MCs were found in all cases. There was an increase in LCs density irrespective of degree of ED when
the cases were compared to normal lip mucosa (P = 0.04343). No statistical difference in LCs density was observed regarding the different degrees of dysplasia (P > 0.05). Significant difference in MCs density between mild and moderate dysplasia and normal lip mucosa was found (P < 0.05). No significant correlation between LCs and MCs was seen (P = 0.1258). Although no correlation could be established between LCs and MCs and the different degrees of ED; it is possible
that the accumulation of LCs plays an immunostimulatory and protective role in the defense against progression of dysplasia.
Further studies are necessary to determine the role of MCs in the development of AC. 相似文献