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91.
Nair MP Kandaswami C Mahajan S Chadha KC Chawda R Nair H Kumar N Nair RE Schwartz SA 《Biochimica et biophysica acta》2002,1593(1):29-36
Flavonoids are plant metabolites that are dietary antioxidants and exert significant anti-tumor, anti-allergic, anti-inflammatory and anti-viral effects. It is generally accepted that Th-1 derived cytokines such as IL-2, IFNgamma and IL-12 promote cellular immunity while Th-2 derived cytokines such as IL-4, IL-5, IL-6 exert negative immunoregulatory effects on cellular immunity while upregulating humoral immunity. The molecular mechanisms underlying the biological activities of flavonoids have not been elucidated. We hypothesize that the flavonoid, quercetin, exert significant anti-viral and anti-tumor effects possibly by modulating the production of Th-1 and Th-2 derived cytokines. Peripheral blood mononuclear cells (PBMC, 1 x 10(6) cells/ml) from normal subjects were cultured with different concentrations of quercetin (0.5-50 microM) for 24-72 h and supernates were quantitated for IFN-gamma and IL-4 by ELISA and antiviral activity of IFNgamma by bioassay. FACS analysis was done to determine the number of IFN-gamma and IL-4 positive cells and RT-PCR was done to quantitate gene expression. Quercetin significantly induces the gene expression as well as the production of Th-1 derived IFNgamma and the downregulates Th-2 derived IL-4 by normal PBMC. Further, quercetin treatment increased the phenotypic expression of IFNgamma cells and decreased IL-4 positive cells by FACS analysis, which corroborate with protein secretion and gene expression studies. These results suggest that the beneficial immuno-stimulatory effects of quercetin may be mediated through the induction of Th-1 derived cytokine, IFNgamma, and inhibition of Th-2 derived cytokine, IL-4. 相似文献
92.
Control of lipid composition of membranes is crucial to ensure normal cellular functions. Saccharomyces cerevisiae has two different phosphatidylserine decarboxylase enzymes (Psd1 and Psd2) that catalyze formation of phosphatidylethanolamine. The mitochondrial Psd1 provides roughly 70% of the phosphatidylethanolamine (PE) biosynthesis in the cell with Psd2 carrying out the remainder. Here, we demonstrate that loss of Psd2 causes cells to acquire sensitivity to cadmium even though Psd1 remains intact. This cadmium sensitivity results from loss of normal activity of a vacuolar ATP-binding cassette transporter protein called Ycf1. Measurement of phospholipid levels indicates that loss of Psd2 causes a specific reduction in vacuolar membrane PE levels, whereas total PE levels are not significantly affected. The presence of a phosphatidylinositol transfer protein called Pdr17 is required for Psd2 function and normal cadmium tolerance. We demonstrate that Pdr17 and Psd2 form a complex in vivo that seems essential for maintenance of vacuolar PE levels. Finally, we refine the localization of Psd2 to the endosome arguing that this enzyme controls vacuolar membrane phospholipid content by regulating phospholipids in compartments that will eventually give rise to the vacuole. Disturbance of this regulation of intracellular phospholipid balance leads to selective loss of membrane protein function in the vacuole. 相似文献
93.
Rationale
Oxygen therapy improves survival and function in severely hypoxemic chronic obstructive pulmonary disease (COPD) patients based on two landmark studies conducted over 40 years ago. We hypothesize that oxygen users in the current era may be very different. We examined trends and subject characteristics associated with oxygen therapy use from 2001–2010 in the United States.Methods
We examined Medicare beneficiaries with COPD who received oxygen from 2001 to 2010. COPD subjects were identified by: 1) ≥2 outpatient visits >30 days apart within one year with an encounter diagnosis of COPD; or 2) an acute care hospitalization with COPD as the primary or secondary discharge diagnosis. Oxygen therapy and sustained oxygen therapy were defined as ≥1 and ≥11 claims for oxygen, respectively, in the durable medical equipment file in a calendar year. Primary outcome measures were factors associated with oxygen therapy and sustained oxygen therapy over the study period.Results
Oxygen therapy increased from 33.7% in 2001 to 40.5% in 2010 (p-value of trend <0.001). Sustained oxygen therapy use increased from 19.5% in 2001, peaked in 2008 to 26.9% and declined to 18.5% in 2010. The majority of subjects receiving oxygen therapy and sustained oxygen therapy were female. Besides gender, factors associated with any oxygen use or sustained oxygen therapy were non-Hispanic white race, low socioeconomic status and ≥2 comorbidities.Conclusions
Any oxygen use among fee-for service Medicare beneficiaries with COPD is high. Current users of oxygen are older females with multiple comorbidities. Decline in sustained oxygen therapy use after 2008 may be related to reimbursement policy change. 相似文献94.
Sumbul Firdaus Anupam Dhasmana Vandana Srivastava Tasneem Bano Afreen Fatima Qazi Mohammad Sajid Jamal Roshan Jahan Gulshan Wadhwad Mohtashim Lohani 《Bioinformation》2015,11(3):122-126
Fullerenes have attracted considerable attention due to their unique chemical structure and potential applications which has
opened wide venues for possible human exposure to various fullerene types. Therefore, in depth knowledge of how fullerene may
interfere with various cellular processes becomes quite imperative. The present study was designed to investigate how the
presence of fullerene affect the binding of DNA with different enzymes involved in replication process. Different fullerenes were
first docked with DNA and then binding scores of different enzymes was analyzed with fullerene docked DNA. C30, C40 & C50
once docked with DNA, reduced the binding score of primase, whereas no significant change in the binding score was observed
with the helicase, ssb protein, dna pol δ, dna pol ε, ligase, DNA clamp, and topoisomerases. On the contrast, the binding score of
RPA14 decreases in fluctuating manner while interacting with increasing molecular weight of fullerene bound single-stranded
DNA complex. The study revealed the affect of fullerene family interacting with DNA on the binding pattern of enzymes involved
in replication process. Study suggests that the presence of most of fullerenes may not affect the activity of these enzymes necessary
for replication process whereas C30, C40 & C50 may disrupt the activity of primase, (strating point for DNA polymerase) its
docking score decreases from 13820 to 10702. 相似文献
95.
Partha Pratim Manna Sumit Kumar Hira Apabrita Ayan Das Santu Bandyopadhyay Kailash Kumar Gupta 《Cytokine》2013,61(1):118-126
IL-15 is a pleotropic cytokine, which plays an important role in natural killer (NK) cell activity, T cell proliferation, and T cell cytotoxic activity. Dendritic cells (DCs) are the major antigen presenting cells in the immune system and presumed to play an important role in immune recognition of allo and xenotransplantation. We showed that IL-15 activated human peripheral blood DC is cytotoxic to human and porcine aortic endothelial cells. Unlike DCs, CD14+ monocytes show no cytotoxicity against the endothelial cells. This cytotoxic potential of IL-15 activated DC against endothelial cells is dose dependent and increases significantly upon treatment of endothelial cells with inflammatory cytokines like TNF-α or IFN-γ. The cytotoxic potential of IL-15 activated DC is associated with apoptosis of endothelial cells, as indicated by the increased Annexin V staining, caspase activation and loss of mitochondrial membrane potential. Further it was observed that DC mediated cytotoxicity against endothelial cell is mediated via granzyme B possibly secreted by the activated DCs. 相似文献
96.
Brijesh Rathi Anil K. Singh Ram Kishan Neelu Singh N. Latha S. Srinivasan Kailash C. Pandey Hemandra K. Tiwari Brajendra K. Singh 《Bioorganic & medicinal chemistry》2013,21(17):5503-5509
Self-assembled peptide based nanostructures gained enough popularity due to their easy biocompatibility and numerous potential applications. An excellent model of self-assembly of hydroxyethylamine based peptide nanostructures was synthesized and characterized by DLS and TEM. Spherical nano structures of I and III were observed with particle size ~50 and ~80 nm, respectively. Further, I and III were screened against anti-malarial target, falcipain-3 (FP3), a crucial cysteine protease involved as a major hemoglobinase of Plasmodium falciparum. Interestingly, compound III completely inhibited the activity of FP3. The effective concentration (1.5 μM) of III found to be more potent than I. This biochemical result was substantiated by molecular-docking studies indicating III to be best inhibitor of FP3. This is the first report showing that bis hydroxethylamine based peptide nanostructures could be very effective inhibitor of malarial cysteine proteases. 相似文献
97.
Chandrabhan Seniya Harshal Mishra Ajay Yadav Nitin Sagar Babita Chaturvedi Kuldeep Uchadia Gulshan Wadhwa 《Bioinformation》2013,9(1):54-60
4-hydroxypanduratin A is a secondary metabolite of Boesenbergia pandurata Schult. (Fingerroot) plant with various pharmacological
activities such as neuroprotective, potent antioxidant, antibacterial and antifungal. Flaviviral NS2B/NS3 protease activity is
essential for polyprotein processing and viral replication for Japanese Encephalitis Virus (JEV), a major cause of Acute Encephaltis in
Asia. Inhibition of formation of this complex by arresting the binding of NS2B with NS3 would reduce the enzyme''s activity to
meager proportions and hence would prevent further viral proliferation. The automated 3D structure of NS2B protein of the JEV
GP78 was predicted based on the sequence-to-structure-to-function paradigm using I-TASSER and the function of NS2B protein
was inferred by matching to other known proteins. The stereochemical quality of predicted structure was checked by PROCHECK.
The antiviral activity of 4-hydroxypanduratin A against NS2B protein as a potential drug has been elucidated in this paper.
Docking simulation analysis showed 4-hydroxypanduratin A as potential inhibitor of NS2B protein/cofactor which is necessary for
NS3 protease activity. 220 derivatives of 4-hydroxypanduratin A were virtually screened with rigid criteria of Lipinski''s rule of 5
using Autodock4.2. 4-hydroxypanduratin A was found interacting with target hydrophilic domain in NS2B protein by two Hbonds
(Gly80 and Asp81) with active residues, several hydrophobic interactions, Log P value of 5.6, inhibition constant (Ki) of
51.07nM and lowest binding energy of -9.95Kcal/Mol. Hence, 4-hydroxypanduratin A targeted to Site 2 will have sufficient
profound effect to inhibit protease activity to abrogate viral replication. It could be a promising potential drug candidate for JEV
infections using NS2B Site 2 as a Drug target. 相似文献
98.
99.
Several pieces of evidence indicate that global climate change is affecting biological systems all across the world. Phenology
is one of the tools that may indicate changing patterns. The paper focuses on the phenological pattern of alpine/sub-alpine
species Aconitum heterophyllum, a high-value medicinal herb of the Indian Himalayan Region (IHR), a global hotspot and known to be sensitive to climatic
change. In all 117 herbarium specimens of the species collected from three provinces (Western Himalaya, North West Himalaya
and Trans Himalaya) of the region were recorded. Historic herbarium records (1848–2003) were analyzed to predict the flowering
patterns using Generalized Additive Model (GAM) in view of complexity in the herbarium-based data structure. GAM indicated
that the flowering time responded significantly, 26 days earlier per 1,000 m (P < 0.02). Likewise, the model showed significantly earlier flowering (17–25 days) during the last 100 years (P < 0.01). Moreover, maximum temperature of winter (December–February) explained increasing trends at both elevations (lower
and mid) and mean winter temperature influenced the early flowering time (19–27 days) with an increase of 1°C. The overall
early flowering of A. heterophyllum may perhaps be considered as indicator of climate change; however, more datasets of herbarium records are required to further
strengthen this premise. This study was undertaken to show that herbarium records could be utilized as a potential resource
for assessing climate change using GAM. 相似文献
100.