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51.
52.
Background
Insulin resistance and type 2 diabetes are more prevalent in people of South Asian ethnicity than in people of Western European origin. To investigate the source of these differences, we compared insulin sensitivity, insulin secretion, glucose and lipid metabolism in South Asian and Nordic subjects with type 2 diabetes.Methods
Forty-three Nordic and 19 South Asian subjects with type 2 diabetes were examined with intra-venous glucose tolerance test, euglycemic clamp including measurement of endogenous glucose production, indirect calorimetry measuring glucose and lipid oxidation, and dual x-ray absorptiometry measuring body composition.Results
Despite younger mean ± SD age (49.7±9.4 vs 58.3±8.3 years, p = 0.001), subjects of South Asian ethnicity had the same diabetes duration (9.3±5.5 vs 9.6±7.0 years, p = 0.86), significantly higher median [inter-quartile range] HbA1c (8.5 [1.6] vs 7.3 [1.6] %, p = 0.024) and lower BMI (28.7±4.0 vs 33.2±4.7 kg/m2, p<0.001). The South Asian group exhibited significantly higher basal endogenous glucose production (19.1 [9.1] vs 14.4 [6.8] µmol/kgFFM⋅min, p = 0.003). There were no significant differences between the groups in total glucose disposal (39.1±20.4 vs 39.2±17.6 µmol/kgFFM⋅min, p = 0.99) or first phase insulin secretion (AUC0–8 min: 220 [302] vs 124 [275] pM, p = 0.35). In South Asian subjects there was a tendency towards positive correlations between endogenous glucose production and resting and clamp energy expenditure.Conclusions
Subjects of South Asian ethnicity with type 2 diabetes, despite being younger and leaner, had higher basal endogenous glucose production, indicating higher hepatic insulin resistance, and a trend towards higher use of carbohydrates as fasting energy substrate compared to Nordic subjects. These findings may contribute to the understanding of the observed differences in prevalence of type 2 diabetes between the ethnic groups. 相似文献53.
Wirths O Erck C Martens H Harmeier A Geumann C Jawhar S Kumar S Multhaup G Walter J Ingelsson M Degerman-Gunnarsson M Kalimo H Huitinga I Lannfelt L Bayer TA 《The Journal of biological chemistry》2010,285(53):41517-41524
N-terminally truncated Aβ peptides starting with pyroglutamate (AβpE3) represent a major fraction of all Aβ peptides in the brain of Alzheimer disease (AD) patients. AβpE3 has a higher aggregation propensity and stability and shows increased toxicity compared with full-length Aβ. In the present work, we generated a novel monoclonal antibody (9D5) that selectively recognizes oligomeric assemblies of AβpE3 and studied the potential involvement of oligomeric AβpE3 in vivo using transgenic mouse models as well as human brains from sporadic and familial AD cases. 9D5 showed an unusual staining pattern with almost nondetectable plaques in sporadic AD patients and non-demented controls. Interestingly, in sporadic and familial AD cases prominent intraneuronal and blood vessel staining was observed. Using a novel sandwich ELISA significantly decreased levels of oligomers in plasma samples from patients with AD compared with healthy controls were identified. Moreover, passive immunization of 5XFAD mice with 9D5 significantly reduced overall Aβ plaque load and AβpE3 levels, and normalized behavioral deficits. These data indicate that 9D5 is a therapeutically and diagnostically effective monoclonal antibody targeting low molecular weight AβpE3 oligomers. 相似文献
54.
Claudia Hoffmann Alfred Blume Inge Miller Patrick Garidel 《European biophysics journal : EBJ》2009,38(5):557-568
Therapeutic proteins formulated as liquid solutions at high protein concentration are very sensitive to chemical and physical
degradation. Especially avoiding the formation of protein aggregates is very crucial for product quality. In order to stabilize
the colloidal properties of protein therapeutics various excipient are used. Especially the detergents polysorbate 20 and
80 are common. However, the mechanism upon which the detergents protect the protein from aggregation is not really known.
The present study investigates the interaction of polysorbate 20 and 80 with different proteins: lysozyme, bovine serum albumin
(BSA) and an immunoglobulin. The interaction and binding of the detergents to the proteins is investigated by isothermal titration
calorimetry (ITC). From ITC the thermodynamic parameters (ΔH: change in enthalpy, ΔS: entropy and ΔG: free energy) upon binding are derived as well as the binding constant K
a. The thermal stability of the proteins in the presence of the detergent is assessed by differential scanning calorimetry
(DSC). The results show that both detergents bind to BSA with K
a between 8 and 12 × 103 M−1 with ΔH −50 to −60 kJ/mol (25°C). One to two detergent molecules bind to BSA. The presence of both detergents induces a weak stabilisation
of the thermal denaturation properties of BSA. However, the interaction of polysorbate 20 and 80 with lysozyme and the immunoglobulin
is quite negligible. The presence of the detergents up to a concentration of 2 mM has no impact on the heat capacity curve
neither a destabilisation nor a stabilisation of the native conformation is observed. 相似文献
55.
With the growing interest in the use of metabolomic technologies for a wide range of biological targets, food applications related to nutrition and quality are rapidly emerging. Metabolomics offers us the opportunity to gain deeper insights into, and have better control of, the fundamental biochemical basis of the things we eat. So doing will help us to design modified breeding programmes aimed at better quality produce; optimised food processing strategies and ultimately, improved (micro)nutrient bioavailability and bioefficacy. A better understanding of the pathways responsible for the biosynthesis of nutritionally relevant metabolites is key to gaining more effective control of the absence/level of presence of such components in our food. Applications of metabolomic technologies in both applied and fundamental science strategies are therefore growing rapidly in popularity. Currently, the world has two highly contrasting nutrition-related problems--over-consumption and under-nourishment. Dramatic increases in the occurrence of overweight individuals and obesity in developed countries are in staggering contrast to the still-familiar images of extreme malnutrition in many parts of the developing world. Both problems require a modified food supply, achieved through highly contrasting routes. For each, metabolomics has a future role to play and this review shall deal with this key dichotomy and illustrate where metabolomics may have a future part to play. In this short overview, attention is given to how the various technologies have already been exploited in a plant-based food context related to key issues such as biofortification, bioprotectants and the general link between food composition and human health. Research on key crops such as rice and tomato are used as illustration of potentially broader application across crop species. Although the focus is clearly on food supply, some attention is given to the complementary field of research, nutrigenomics, where similar technologies are being applied to understand nutrition better from the human side. 相似文献
56.
Doris Ribitsch Sonja Heumann Eva Trotscha Enrique Herrero Acero Katrin Greimel Regina Leber Ruth Birner‐Gruenberger Sigrid Deller Inge Eiteljoerg Peter Remler Thomas Weber Petra Siegert Karl‐Heinz Maurer Ilaria Donelli Giuliano Freddi Helmut Schwab Georg M. Guebitz 《Biotechnology progress》2011,27(4):951-960
From a screening on agar plates with bis(benzoyloxyethyl) terephthalate (3PET), a Bacillus subtilis p‐nitrobenzylesterase (BsEstB) was isolated and demonstrated to hydrolyze polyethyleneterephthalate (PET). PET‐hydrolase active strains produced clearing zones and led to the release of the 3PET hydrolysis products terephthalic acid (TA), benzoic acid (BA), 2‐hydroxyethyl benzoate (HEB), and mono‐(2‐hydroxyethyl) terephthalate (MHET) in 3PET supplemented liquid cultures. The 3PET‐hydrolase was isolated from non‐denaturating polyacrylamide gels using fluorescein diacetate (FDA) and identified as BsEstB by LC‐MS/MS analysis. BsEstB was expressed in Escherichia coli with C‐terminally fused StrepTag II for purification. The tagged enzyme had a molecular mass of 55.2 kDa and a specific activity of 77 U/mg on p‐nitrophenyl acetate and 108 U/mg on p‐nitrophenyl butyrate. BsEstB was most active at 40°C and pH 7.0 and stable for several days at pH 7.0 and 37°C while the half‐life times decreased to 3 days at 40°C and only 6 h at 45°C. From 3PET, BsEstB released TA, MHET, and BA, but neither bis(2‐hydroxyethyl) terephthalate (BHET) nor hydroxyethylbenzoate (HEB). The kcat values decreased with increasing complexity of the substrate from 6 and 8 (s?1) for p‐nitrophenyl‐acetate (4NPA) and p‐nitrophenyl‐butyrate (4NPB), respectively, to 0.14 (s?1) for bis(2‐hydroxyethyl) terephthalate (BHET). The enzyme hydrolyzed PET films releasing TA and MHET with a concomitant decrease of the water‐contact angle (WCA) from 68.2° ± 1.7° to 62.6° ± 1.1° due to formation of novel hydroxyl and carboxyl groups. These data correlated with a fluorescence emission intensity increase seen for the enzyme treated sample after derivatization with 2‐(bromomethyl)naphthalene. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011 相似文献
57.
Nungki Anggorowati Yoshihiko Yano Yanri Wijayanti Subronto Takako Utsumi Didik Setyo Heriyanto Deshinta Putri Mulya Hanggoro Tri Rinonce Dewiyani Indah Widasari Maria Inge Lusida Soetjipto Yoshitake Hayashi 《Microbiology and immunology》2013,57(4):298-308
GB virus C (GBV‐C), a human virus of the Flaviviridae family that is structurally and epidemiologically closest to hepatitis C virus (HCV), has been reported to confer beneficial outcomes in HIV‐positive patients. However, the prevalence of GBV‐C in HIV‐positive individuals in Indonesia is unknown. Since GBV‐C is more prevalent in anti‐HCV positive patients than in anti‐HCV negative subjects, transmission of GBV‐C and HCV could be by the same method. This study examined the prevalence and molecular characteristics of GBV‐C infection in HIV patients in Yogyakarta, Indonesia. The prevalence of GBV‐C among HIV patients (n = 125, median age 31 years) based on the 5′UTR region was 111/125 (88.8%), including 39/48 (81.3%) and 72/77 (93.5%) HIV‐infected patients with and without HCV infection, respectively. GBV‐C isolates were of genotype 2a, 3 and 6 in 58.3%, 12.6% and 28.4% of patients, respectively. Patients with genotype 3 were significantly younger than those with genotypes 2a or 6 (P = 0.001 and P = 0.012, respectively). Genotypes 3 and 6 were significantly associated with injection drug use (P = 0.004 and P = 0.002, respectively) and HCV co‐infection (P < 0.001 for both genotypes), indicating a shared transmission route with HCV. In conclusion, the prevalence of GBV‐C among HIV‐positive patients in Indonesia is high, and three genotypes were detected, namely genotype 2a, 3 and 6. 相似文献
58.
Yara Koréissi-Dembélé Nadia Fanou-Fogny Diego Moretti Stephan Schuth Romain A. M. Dossa Ines Egli Michael B. Zimmermann Inge D. Brouwer 《PloS one》2013,8(10)
Low iron and high phytic acid content make fonio based meals a poor source of bioavailable iron. Phytic acid degradation in fonio porridge using whole grain cereals as phytase source and effect on iron bioavailability when added to iron fortified fonio meals were investigated. Grains, nuts and seeds collected in Mali markets were screened for phytic acid and phytase activity. We performed an iron absorption study in Beninese women (n = 16), using non-dephytinised fonio porridge (FFP) and dephytinised fonio porridge (FWFP; 75% fonio-25% wheat), each fortified with 57Fe or 58Fe labeled FeSO4. Iron absorption was quantified by measuring the erythrocyte incorporation of stable iron isotopes. Phytic acid varied from 0.39 (bambara nut) to 4.26 g/100 g DM (pumpkin seed), with oilseeds values higher than grains and nuts. Phytase activity ranged from 0.17±1.61 (fonio) to 2.9±1.3 phytase unit (PU) per g (whole wheat). Phytic acid was almost completely degraded in FWFP after 60 min of incubation (pH≈5.0, 50°C). Phytate∶iron molar ratios decreased from 23.7∶1 in FFP to 2.7∶1 in FWFP. Iron fortification further reduced phytate∶iron molar ratio to 1.9∶1 in FFP and 0.3∶1 in FWFP, respectively. Geometric mean (95% CI) iron absorption significantly increased from 2.6% (0.8–7.8) in FFP to 8.3% (3.8–17.9) in FWFP (P<0.0001). Dephytinisation of fonio porridge with intrinsic wheat phytase increased fractional iron absorption 3.2 times, suggesting it could be a possible strategy to decrease PA in cereal-based porridges. 相似文献
59.
Alonso Adel C Mederlyova A Novak M Grundke-Iqbal I Iqbal K 《The Journal of biological chemistry》2004,279(33):34873-34881
Mutations in the tau gene are known to cosegregate with the disease in frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). However, the molecular mechanism by which these mutations might lead to the disease is not understood. Here, we show that four of the FTDP-17 tau mutations, R406W, V337M, G272V, and P301L, result in tau proteins that are more favorable substrates for phosphorylation by brain protein kinases than the wild-type, largest four-repeat protein tau4L and tau4L more than tau3L. In general, at all the sites studied, mutant tau proteins were phosphorylated faster and to a higher extent than tau4L and tau4L > tau3L. The most dramatic difference found was in the rate and level of phosphorylation of tau4L(R406W) at positions Ser-396, Ser-400, Thr-403, and Ser-404. Phosphorylation of this mutant tau was 12 times faster and 400% greater at Ser-396 and less than 30% at Ser-400, Thr-403, and Ser-404 than phosphorylation of tau4L. The mutated tau proteins polymerized into filaments when 4-6 mol of phosphate per mol of tau were incorporated, whereas wild-type tau required approximately 10 mol of phosphate per mol of protein to self-assemble. Mutated and wild-type tau proteins were able to sequester normal tau upon incorporation of approximately 4 mol of phosphate per mol of protein, which was achieved at as early as 30 min of phosphorylation in the case of mutant tau proteins. These findings taken together suggest that the mutations in tau might cause neurodegeneration by making the protein a more favorable substrate for hyperphosphorylation. 相似文献
60.
Kieffer TL De Meyer S Bartels DJ Sullivan JC Zhang EZ Tigges A Dierynck I Spanks J Dorrian J Jiang M Adiwijaya B Ghys A Beumont M Kauffman RS Adda N Jacobson IM Sherman KE Zeuzem S Kwong AD Picchio G 《PloS one》2012,7(4):e34372