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951.
Ha Nguyen Thi Thu Quan Pham Minh Cuong Pham Van Tuyen Nguyen Van Kiem Phan Van Tra Nguyen Thanh Anh Le Thi Tu Marc Litaudon Son Ninh The 《化学与生物多样性》2021,18(11):e2100396
A new racemic xanthone, garmckeanin A ( 1 ), and eight known analogs 2 – 9 were isolated from the ethyl acetate (AcOEt) extract of the Vietnamese Garcinia mckeaniana leaves. Their structures were determined by MS and NMR spectral analyses and compared with the literature. The AcOEt extract showed good cytotoxicity against cancer cell lines KB, Lu, Hep-G2 and MCF7, with IC50 values of 5.40–8.76 μg/mL, and it also possessed α-glucosidase inhibitory activity, with an IC50 value of 9.17 μg/mL. Garmckeanin A ( 1 ) exhibited inhibition of all cancer cell lines, with an IC50 value of 7.3–0.9 μM. Allanxanthone C ( 5 ) successfully controlled KB growth, with an IC50 value of 0.54 μM, higher than that of the positive control, ellipticine (IC50 1.22 μM). Norathyriol ( 8 ) was a promising α-glucosidase inhibitor, with an IC50 value of 0.07 μM, much higher than that of the positive control, acarbose (IC50 161.0 μM). The interactions of the potential α-glucosidase inhibitors with the C- and N-terminal domains of human intestinal α-glucosidase were also investigated by molecular docking study. The results indicated that bannaxanthone D ( 2 ), garcinone E ( 4 ), bannaxanthone E ( 6 ), and norathyriol ( 8 ) exhibit higher binding affinity to the C-terminal than to the N-terminal domain through essential residues in the active sites. In particular, compound 8 could be assumed to be the most potent mixed inhibitor. 相似文献
952.
成功构建pET-24a-tscd质粒,实现Thermococcus sp.Strain B1001来源的环糊精酶(TsCDase)在Es-cherichia coli BL21(DE3)中表达.通过热处理和镍柱分离对重组TsCDase进行纯化.酶学性质研究表明,重组TsCDase的比活为1 208.04 U/mg,最适温度为90℃、最适pH值为5.5.重组酶TsCDase在85℃、90℃、95℃条件下的半衰期分别为180、120、30min.酶转化研究表明,以80 g/L β-环糊精为底物,当酶转化温度为90℃、反应pH值为5.5~6.0,加酶量为25 U/g,反应时间为4 h时,麦芽七糖产率为81.19%和85.95%,七糖占产物麦芽寡糖的比例为95.24%和92.92%.本研究结果为工业化制备麦芽七糖奠定良好基础. 相似文献
953.
954.
Jianchao Quan Carmen S. Ng Harley H. Y. Kwok Ada Zhang Yuet H. Yuen Cheung-Hei Choi Shing-Chung Siu Simon Y. Tang Nelson M. Wat Jean Woo Karen Eggleston Gabriel M. Leung 《PLoS medicine》2021,18(6)
BackgroundExisting predictive outcomes models for type 2 diabetes developed and validated in historical European populations may not be applicable for East Asian populations due to differences in the epidemiology and complications. Despite the continuum of risk across the spectrum of risk factor values, existing models are typically limited to diabetes alone and ignore the progression from prediabetes to diabetes. The objective of this study is to develop and externally validate a patient-level simulation model for prediabetes and type 2 diabetes in the East Asian population for predicting lifetime health outcomes.Methods and findingsWe developed a health outcomes model from a population-based cohort of individuals with prediabetes or type 2 diabetes: Hong Kong Clinical Management System (CMS, 97,628 participants) from 2006 to 2017. The Chinese Hong Kong Integrated Modeling and Evaluation (CHIME) simulation model comprises of 13 risk equations to predict mortality, micro- and macrovascular complications, and development of diabetes. Risk equations were derived using parametric proportional hazard models. External validation of the CHIME model was assessed in the China Health and Retirement Longitudinal Study (CHARLS, 4,567 participants) from 2011 to 2018 for mortality, ischemic heart disease, cerebrovascular disease, renal failure, cataract, and development of diabetes; and against 80 observed endpoints from 9 published trials using 100,000 simulated individuals per trial. The CHIME model was compared to United Kingdom Prospective Diabetes Study Outcomes Model 2 (UKPDS-OM2) and Risk Equations for Complications Of type 2 Diabetes (RECODe) by assessing model discrimination (C-statistics), calibration slope/intercept, root mean square percentage error (RMSPE), and R2. CHIME risk equations had C-statistics for discrimination from 0.636 to 0.813 internally and 0.702 to 0.770 externally for diabetes participants. Calibration slopes between deciles of expected and observed risk in CMS ranged from 0.680 to 1.333 for mortality, myocardial infarction, ischemic heart disease, retinopathy, neuropathy, ulcer of the skin, cataract, renal failure, and heart failure; 0.591 for peripheral vascular disease; 1.599 for cerebrovascular disease; and 2.247 for amputation; and in CHARLS outcomes from 0.709 to 1.035. CHIME had better discrimination and calibration than UKPDS-OM2 in CMS (C-statistics 0.548 to 0.772, slopes 0.130 to 3.846) and CHARLS (C-statistics 0.514 to 0.750, slopes −0.589 to 11.411); and small improvements in discrimination and better calibration than RECODe in CMS (C-statistics 0.615 to 0.793, slopes 0.138 to 1.514). Predictive error was smaller for CHIME in CMS (RSMPE 3.53% versus 10.82% for UKPDS-OM2 and 11.16% for RECODe) and CHARLS (RSMPE 4.49% versus 14.80% for UKPDS-OM2). Calibration performance of CHIME was generally better for trials with Asian participants (RMSPE 0.48% to 3.66%) than for non-Asian trials (RMPSE 0.81% to 8.50%). Main limitations include the limited number of outcomes recorded in the CHARLS cohort, and the generalizability of simulated cohorts derived from trial participants.ConclusionsOur study shows that the CHIME model is a new validated tool for predicting progression of diabetes and its outcomes, particularly among Chinese and East Asian populations that has been lacking thus far. The CHIME model can be used by health service planners and policy makers to develop population-level strategies, for example, setting HbA1c and lipid targets, to optimize health outcomes.In a modelling study, Jianchao Quan and colleagues develop and validate a novel prediabetes and type 2 diabetes outcomes prediction model for Chinese and East Asian populations. 相似文献
955.
Zhang LJ Zhang LJ Quan W Wang BB Shen BL Zhang TT Kang Y 《Journal of microbiology (Seoul, Korea)》2011,49(5):834-840
This study investigated the inhibitory effects of berberine on Chlamydophila (Chlamydia) pneumoniae infection-induced HEp-2 cell invasion and explored the possible mechanisms involved in this process. C. pneumoniae infection resulted in a significant increase in HEp-2 cell invasion when compared with the control cells (P<0.01) in a Matrigel
invasion assay. This enhanced cell invasion was strongly suppressed by berberine (50 μM) (P<0.01). In a cell adhesion assay,
the infection-induced HEp-2 cell adhesion to Matrigel was also significantly inhibited by berberine (P<0.01). C. pneumoniae infection was found to promote HEp-2 cell migration remarkably (P<0.01), which was markedly suppressed by berberine (P<0.01)
in the cell migration assays. There were no statistically significant differences in the expression of matrix metalloproteinase-1
(MMP-1) and MMP-9 in the infected cells and berberine did not change the expression of MMP-1 and MMP-9. These data suggest
that berberine inhibits C. pneumoniae infection-induced HEp-2 cell invasion through suppressing HEp-2 cell adhesion and migration, but not through changing the
expression of MMP-1 and MMP-9. 相似文献
956.
Tissue inhibitor of metalloproteinase-1 promotes NIH3T3 fibroblast proliferation by activating p-Akt and cell cycle progression 总被引:1,自引:0,他引:1
Lu Y Liu S Zhang S Cai G Jiang H Su H Li X Hong Q Zhang X Chen X 《Molecules and cells》2011,31(3):225-230
Tissue inhibitor of metalloproteinase-1 (TIMP-1) plays various roles in cell growth in different cell types. However, few
studies have focused on TIMP-1’s effect on fibroblast cells. In this study, we investigated the effects of TIMP-1 overexpression
on NIH3T3 fibroblast proliferation and potential transduction signaling pathways involved. Overexpression of TIMP-1, by transfection
of the pLenti6/V5-DESTTIMP-1 plasmid, significantly promoted NIH3T3 proliferation as determined by the BrdU array. Neither
5 nor 15 nM GM6001 (matrix metalloproteinase system inhibitor) affected NIH3T3 proliferation, but 45 nM GM6001 inhibited proliferation.
TIMP-1 overexpression activated the p-Akt pathway, but not the p-ERK or p-p38 pathway. In TIMP-1-transfected cells, cyclinD1
was upregulated and p21CIP1 and p27KIP1 were downregulated, which promoted cell entry into the S and G2/M phases. The PI3-K inhibitor LY294002 abolished the TIMP-1-induced
effects. Overexpression of intracellular TIMP-1 stimulated NIH3T3 fibroblast proliferation in a matrix metalloproteinase (MMP)-independent
manner by activating the p-Akt pathway and related cell cycle progression. 相似文献
957.
958.
Li QZ Karp DR Quan J Branch VK Zhou J Lian Y Chong BF Wakeland EK Olsen NJ 《Arthritis research & therapy》2011,13(2):R38
Introduction
The finding of antinuclear antibody (ANA) positivity in a healthy individual is usually of unknown significance and in most cases is benign. However, a subset of such individuals is at risk for development of autoimmune disease. We examined demographic and immunological features that are associated with ANA positivity in clinically healthy persons to develop insights into when this marker carries risk of progression to lupus. 相似文献959.
Ju S Tardiff DF Han H Divya K Zhong Q Maquat LE Bosco DA Hayward LJ Brown RH Lindquist S Ringe D Petsko GA 《PLoS biology》2011,9(4):e1001052
FUS/TLS is a nucleic acid binding protein that, when mutated, can cause a subset of familial amyotrophic lateral sclerosis (fALS). Although FUS/TLS is normally located predominantly in the nucleus, the pathogenic mutant forms of FUS/TLS traffic to, and form inclusions in, the cytoplasm of affected spinal motor neurons or glia. Here we report a yeast model of human FUS/TLS expression that recapitulates multiple salient features of the pathology of the disease-causing mutant proteins, including nuclear to cytoplasmic translocation, inclusion formation, and cytotoxicity. Protein domain analysis indicates that the carboxyl-terminus of FUS/TLS, where most of the ALS-associated mutations are clustered, is required but not sufficient for the toxicity of the protein. A genome-wide genetic screen using a yeast over-expression library identified five yeast DNA/RNA binding proteins, encoded by the yeast genes ECM32, NAM8, SBP1, SKO1, and VHR1, that rescue the toxicity of human FUS/TLS without changing its expression level, cytoplasmic translocation, or inclusion formation. Furthermore, hUPF1, a human homologue of ECM32, also rescues the toxicity of FUS/TLS in this model, validating the yeast model and implicating a possible insufficiency in RNA processing or the RNA quality control machinery in the mechanism of FUS/TLS mediated toxicity. Examination of the effect of FUS/TLS expression on the decay of selected mRNAs in yeast indicates that the nonsense-mediated decay pathway is probably not the major determinant of either toxicity or suppression. 相似文献
960.
The present investigation was undertaken with the objective of developing a solid formulation containing nitrendipine nanocrystals
for oral delivery. Nitrendipine nanocrystals were prepared using a tandem precipitation–homogenization process. Then, spray
drying, a cost-effective method very popular in industrial situations, was employed to convert the nanocrystals into a solid
form. The parameters of the preparation process were investigated and optimized. The optimal process was as follows: firstly,
nitrendipine/acetone solution (100 mg/ml) was added to a polyvinyl alcohol solution (1 mg/ml) at 10°C, then the pre-suspension
was homogenized for 20 cycles at 1,000 bar. Both differential scanning calorimetry and X-ray diffraction analysis indicated
that nitrendipine was present in crystalline form. The in vitro dissolution rate of the nanocrystals was significantly increased compared with the physical mixture and commercial tablet.
The in vivo testing demonstrated that the C
max of the nanocrystals was approximately 15-fold and 10-fold greater than that of physical mixture and commercial tablet, respectively.
In addition, the AUC0→24 of the nanocrystals was approximately 41-fold and 10-fold greater than that of physical mixture and commercial tablet, respectively. 相似文献