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Ankita Deb Bhavana Deshmukh Pranay Ramteke Firoz Khan Bhati Manoj Kumar Bhat 《Translational oncology》2021,14(10)
Resistin, a small secretory molecule, has been implicated to play an important role in the development of insulin resistance under obese condition. For the past few decades, it has been linked to various cellular and metabolic functions. It has been associated with diseases like metabolic disorders, cardiovascular diseases and cancers. Numerous clinical studies have indicated an increased serum resistin level in pathological disorders which have been reported to increase mortality rate in comparison to low resistin expressing subjects. Various molecular studies suggest resistin plays a pivotal role in proliferation, metastasis, angiogenesis, inflammation as well as in regulating metabolism in cancer cells. Therefore, understanding the role of resistin and elucidating its’ associated molecular mechanism will give a better insight into the management of these disorders. In this article, we summarize the diverse roles of resistin in pathological disorders based on the available literature, clinicopathological data, and a compiled study from various databases. The article mainly provides comprehensive information of its role as a target in different treatment modalities in pre as well as post-clinical studies. 相似文献
44.
Apoptosis in macrophages is responsible for immune-depression and pathological effects during malaria. Phagocytosis of PRBC causes induction of apoptosis in macrophages through release of cytosolic factors from infected cells. Heme polymer or β-hematin causes dose-dependent death of macrophages with LC50 of 132 µg/ml and 182 µg/ml respectively. The toxicity of hemin or heme polymer was amplified several folds in the presence of non-toxic concentration of methemoglobin. β-hematin uptake in macrophage through phagocytosis is crucial for enhanced toxicological effects in the presence of methemoglobin. Higher accumulation of β-hematin is observed in macrophages treated with β-hematin along with methemoglobin. Light and scanning electron microscopic observations further confirm accumulation of β-hematin with cellular toxicity. Toxicological potentiation of pro-oxidant molecules toward macrophages depends on generation of H2O2 and independent to release of free iron from pro-oxidant molecules. Methemoglobin oxidizes β-hematin to form oxidized β-hematin (βH*) through single electron transfer mechanism. Pre-treatment of reaction mixture with spin-trap Phenyl-N-t-butyl-nitrone dose-dependently reverses the β-hematin toxicity, indicates crucial role of βH* generation with the toxicological potentiation. Acridine orange/ethidium bromide staining and DNA fragmentation analysis indicate that macrophage follows an oxidative stress dependent apoptotic pathway to cause death. In summary, current work highlights mutual co-operation between methemoglobin and different pro-oxidant molecules to enhance toxicity towards macrophages. Hence, methemoglobin peroxidase activity can be probed for subduing cellular toxicity of pro-oxidant molecules and it may in-turn make up for host immune response against the malaria parasite. 相似文献
45.
Rabbit articular chondrocytes in suspension culture synthesize Type II collagen [3alpha1(II)] in the absence of extracellular Ca2+ and Type I collagen [2alpha1(I) - alpha2] in the complete medium. As a result of pre-treatment in monolayer culture with calcitonin or parathyroid hormone in the complete medium, an influx of Ca2+ into the cells occurs. These cells produce mainly Type I collagen when transferred to suspension cultures in the medium devoid of CaCl2. If added directly to the suspension culture medium containing no CaCl2, calcitonin stimulates an active efflux of Ca2+ from the cells into the medium and leads the cells to synthesize Type I collagen. Under similar conditions, parathyroid hormone does not change the collagen-phenotype. 相似文献
46.
Jennifer L. Jones Sarika Saraswati Ashley S. Block Cheryl F. Lichti Maha Mahadevan Alan B. Diekman 《Glycoconjugate journal》2010,27(2):227-236
Galectin-3 is a β-galactoside-binding protein involved in immunomodulation, cell interactions, cancer progression, and pathogenesis
of infectious organisms. We report the identification and characterization of galectin-3 in human semen. In the male reproductive
tract, the ~30 kDa galectin-3 protein was identified in testis, epididymis, vas deferens, prostate, seminal vesicle, and sperm
protein extracts. In seminal plasma, galectin-3 was identified in the soluble fraction and in prostasomes, cholesterol-rich,
membranous vesicles that are secreted by the prostate and incorporated into seminal plasma during ejaculation. Two-dimensional
immunoblot analysis of purified prostasomes identified five galectin-3 isoelectric variants with a pI range of 7.0 to 9.2.
Affinity purification and tandem mass spectrometry of β-galactoside-binding proteins from prostasomes confirmed the presence
of galectin-3 in prostasomes and identified a truncated galectin-3 variant. The intact galectin-3 molecule contains a carbohydrate
recognition domain and a non-lectin domain that interacts with protein and lipid moieties. The identification of a monovalent
galectin-3 fragment with conserved carbohydrate-binding activity indicates the functional relevance of this truncation and
suggests a regulatory mechanism for galectin-3 in prostasomes. Surface biotinylation studies suggested that galectin-3 and
the truncated galectin-3 variant are localized to the prostasome surface. Prostasomes are proposed to function in immunosuppression
and regulation of sperm function in the female reproductive tract, are implicated in facilitating sexually-transmitted infections,
and are indicated in prostate cancer progression. Given the overlap in functional significance, the identification of galectin-3
in prostasomes lays the groundwork for future studies of galectin-3 and prostasomes in reproduction, disease transmission,
and cancer progression. 相似文献
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Monti DA Mitchell E Bazzan AJ Littman S Zabrecky G Yeo CJ Pillai MV Newberg AB Deshmukh S Levine M 《PloS one》2012,7(1):e29794
Background
Preclinical data support further investigation of ascorbic acid in pancreatic cancer. There are currently insufficient safety data in human subjects, particularly when ascorbic acid is combined with chemotherapy.Methods and Findings
14 subjects with metastatic stage IV pancreatic cancer were recruited to receive an eight week cycle of intravenous ascorbic acid (three infusions per week), using a dose escalation design, along with standard treatment of gemcitabine and erlotinib. Of 14 recruited subjects enrolled, nine completed the study (three in each dosage tier). There were fifteen non-serious adverse events and eight serious adverse events, all likely related to progression of disease or treatment with gemcitabine or erlotinib. Applying RECIST 1.0 criteria, seven of the nine subjects had stable disease while the other two had progressive disease.Conclusions
These initial safety data do not reveal increased toxicity with the addition of ascorbic acid to gemcitabine and erlotinib in pancreatic cancer patients. This, combined with the observed response to treatment, suggests the need for a phase II study of longer duration.Trial Registration
Clinicaltrials.gov NCT00954525相似文献49.
Comparative performance of different scale‐down simulators of substrate gradients in Penicillium chrysogenum cultures: the need of a biological systems response analysis 下载免费PDF全文
50.
Marta Murgia Nagarjuna Nagaraj Atul S Deshmukh Marlis Zeiler Pasqua Cancellara Irene Moretti Carlo Reggiani Stefano Schiaffino Matthias Mann 《EMBO reports》2015,16(3):387-395
Mammalian skeletal muscles are composed of multinucleated cells termed slow or fast fibers according to their contractile and metabolic properties. Here, we developed a high‐sensitivity workflow to characterize the proteome of single fibers. Analysis of segments of the same fiber by traditional and unbiased proteomics methods yielded the same subtype assignment. We discovered novel subtype‐specific features, most prominently mitochondrial specialization of fiber types in substrate utilization. The fiber type‐resolved proteomes can be applied to a variety of physiological and pathological conditions and illustrate the utility of single cell type analysis for dissecting proteomic heterogeneity. 相似文献