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91.
92.
Franke R Hirsch T Eichler J 《Journal of receptor and signal transduction research》2006,26(5-6):453-460
Synthetic mimetics of the CD4-binding site of HIV-1 gp120 are promising candidates for HIV-1 entry inhibition, as well as immunogen candidates for the elicitation of virus-neutralizing antibodies. On the basis of the crystal structure of gp120 in complex with CD4, we have used a recently introduced strategy for the generation of structurally diverse scaffolds to design and synthesize a scaffolded peptide, in which three fragments, making up the sequentially discontinuous binding site of gp120 for CD4, are presented in a nonlinear and discontinuous fashion through a molecular scoffold, which restrains conformational flexibility. The affinities of this molecule to CD4, as well as to the broadly neutralizing antibody mAb b12, whose epitope overlaps the CD4-binding site of gp120, were determined in competitive binding assays. 相似文献
93.
Mariantonia Logozzi Davide Mizzoni Clemente Capasso Sonia Del Prete Rossella Di Raimo Mario Falchi 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):280-288
Abstract Acidity, hypoxia and increased release of exosomes are severe phenotypes of tumours. The regulation of pH in tumours involves the interaction of several proteins, including the carbonic anhydrases which catalyze the formation of bicarbonate and protons from carbon dioxide and water. Among CA isoforms, CA IX is over-expressed in a large number of solid tumours, conferring to cancer cells a survival advantage in hypoxic and acidic microenvironment, but there isn’t evidence that CA IX expression could have a real clinical impact. Therefore, in this study for the first time the expression and activity of CA IX have been investigated in the plasmatic exosomes obtained from patients with prostate carcinoma (PCa). For this purpose, the study was performed through different methodological approaches, such as NTA, western blot analysis, enzyme activity assay, Nanoscale flow cytometry, ELISA, confocal microscopy. The results showed that PCa exosomes significantly overexpressed CA IX levels and related activity as compared to healthy donors. Furthermore, CA IX expression and activity were correlated to the exosome intraluminal pH, demonstrating for the first time that PCa exosomes are acidic. Our data suggest the possible use of the exosomal CA IX expression and activity as a biomarker of cancer progression in PCa. 相似文献
94.
Stefania D’Angelo Francesca Trojsi Anna Salvatore Luca Daniele Marianna Raimo Patrizia Galletti Maria Rosaria Monsurrò 《Neurochemistry international》2013
Spontaneous protein deamidation of labile asparagines (Asn), generating abnormal l-isoaspartyl residues (IsoAsp), is associated with cell aging and enhanced by an oxidative microenvironment. The presence of isopeptide bonds impairs protein structure/function. To minimize the damage, IsoAsp can be “repaired” by the protein l-isoaspartyl/d-aspartyl O-methyltransferase (PIMT) and S-adenosylmethionine (AdoMet) is the methyl donor of this reaction. PIMT is a repair enzyme that initiates the conversion of l-isoAsp (or d-Asp) residues to l-Asp residues. Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease principally affecting motor neurons. The condition of oxidative stress reported in familial and sporadic forms of ALS prompted us to investigate Asn deamidation in ALS tissue. Erythrocytes (RBCs) were selected as a model system since they are unable to replace damaged proteins and protein methylesterification is virtually the only AdoMet-consuming reaction operating in these cells. Our data show that, in vitro assay, abnormal IsoAsp residues were significantly higher in ALS patients erythrocyte membrane proteins with an increased methyl accepting capability relative to controls (p < 0.05). Moreover, we observed a reduction in AdoMet levels, while AdoHcy concentration was comparable to that detected in the control, resulting in a lower [AdoMet]/[AdoHcy] ratio. Then, the accumulation of altered aspartyl residues in ALS patients is probably related to a reduced efficiency of the S-adenosylmethionine (AdoMet)-dependent repair system causing increased protein instability at Asn sites. The increase of abnormal residues represents a new protein alteration that may be present not only in red blood cells but also in other cell types of patients suffering from ALS. 相似文献
95.
Anna‐Maija H. Syrjälä Päivi I. Pussinen Kaija Komulainen Irma Nykänen Matti Knuuttila Piia Ruoppi Sirpa Hartikainen Raimo Sulkava Pekka Ylöstalo 《Gerodontology》2013,30(4):270-275
doi: 10.1111/j.1741‐2358.2012.00679.x Salivary flow rate and risk of malnutrition – a study among dentate, community‐dwelling older people Objective: To analyse the relation between unstimulated and stimulated salivary secretion and the risk of malnutrition among home‐dwelling elderly people. Background: Saliva has an important role in eating. Despite this, there are only a few studies on the role of salivary secretion in the development of malnutrition among elderly people. Materials and methods: The study population consisted of 157 subjects aged 75 or older. This was a part of GeMS study carried out in Kuopio, in eastern Finland. The data used in this study were collected by means of interviews and geriatric and oral clinical examinations. The risk of malnutrition was measured using the Mini Nutritional Assessment Short‐Form. Logistic regression models were used to estimate odds ratios (OR) and their 95% Confidence Intervals (CI). Results: Subjects with a low unstimulated salivary flow rate (<0.1 ml/min) or stimulated salivary flow rate (<1.0 ml/min) had no statistically significant increase in risk of malnutrition, OR: 1.3, CI: 0.5–3.9, OR: 1.5, CI: 0.5–4.2, respectively, when compared with those with a normal unstimulated and stimulated salivary flow rate. Conclusion: Our results do not support the concept that low salivary secretion is an important risk factor for malnutrition among community‐dwelling elders. 相似文献
96.
Lindén J Korkalainen M Lensu S Tuomisto J Pohjanvirta R 《Journal of biochemical and molecular toxicology》2005,19(3):139-148
An acutely toxic dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to a drastically and permanently reduced feed intake and wasting by an unknown mechanism. We focused on the possible interference of TCDD with hypothalamic factors known to take part in the regulation of eating and metabolism, utilizing the over 1000-fold TCDD-sensitivity difference between Long-Evans (Turku/AB; L-E) and Han/Wistar (Kuopio) rats. The mRNA expression of 18 hypothalamic factors (including NPY, AgRP, and CART) was measured by quantitative RT-PCR at 6, 24 and 96 h after TCDD administration. The effects of TCDD were compared with those of leptin and with feed restriction employing a TCDD dose that elicited a severe reduction of feed intake in L-E rats. TCDD mainly modified expression of orexigenic factors causing an initial suppression followed by reversal to enhanced expression by 96 h. The latter was also seen in feed-restricted controls. In contrast, leptin altered both orexigenic and anorexigenic factor mRNAs in a more even manner and its effects were clustered at 6 h. The transient nature of feeding-promoting factor suppression does not strongly support a key role for this phenomenon in TCDD-induced wasting syndrome. However, the fact that TCDD mainly affected orexigenic factors and the temporal differences in response found between the rat strains warrant further research. 相似文献
97.
Mária FízeI'ová Henna Cederberg Alena Stan?áková Raimo Jauhiainen Jagadish Vangipurapu Johanna Kuusisto Markku Laakso 《PloS one》2014,9(10)
We investigated the ability of surrogate markers of tissue-specific insulin resistance (IR, Matsuda IR, Adipocyte IR, Liver IR) to predict deterioration of hyperglycemia, incident type 2 diabetes and cardiovascular events in the Metabolic Syndrome in Men (METSIM) Study. The METSIM Study includes 10,197 Finnish men, aged 45–73 years, and examined in 2005–2010. A total of 558 of 8,749 non-diabetic participants at baseline were diagnosed with new-onset diabetes and 239 with a new CVD event during a 5.9-year follow-up of this cohort (2010–2013). Compared to fasting plasma insulin level, Matsuda IR (IR in skeletal muscle) and Adipocyte IR were significantly better predictors of 2-hour plasma glucose and glucose area under the curve after adjustment for confounding factors. Liver IR was the strongest predictor of both incident type 2 diabetes (hazard ratio = 1.83, 95% confidence interval: 1.68–1.98) and cardiovascular events (hazard ratio = 1.31, 95% confidence interval: 1.15–1.48). Hazard ratios for fasting insulin were 1.37 (95% confidence interval: 1.32–1.42) and 1.11 (95% confidence interval: 1.00–1.24), respectively. Tissue-specific markers of IR, Matsuda IR and Adipocyte IR, were superior to fasting plasma insulin level in predicting worsening of hyperglycemia, and Liver IR was superior to fasting insulin level in predicting incident type 2 diabetes and cardiovascular events. 相似文献
98.
Sillat T Saat R Pöllänen R Hukkanen M Takagi M Konttinen YT 《Journal of cellular and molecular medicine》2012,16(7):1485-1495
During adipogenic differentiation human mesenchymal stem cells (hMSC) produce collagen type IV. In immunofluorescence staining differentiating hMSCs started to express collagen type IV when Oil Red O-positive fat droplets appeared intracellularly. Quantitative real time-polymerase chain reaction confirmed progressive increase of collagen type IV α1 and α2 mRNA levels over time, 18.6- and 12.2-fold by day 28, respectively, whereas the copy numbers of α3-α6 mRNAs remained rather stable and low. Type IV collagen was in confocal laser scanning microscopy seen around adipocytes, where also laminins and nidogen were found, suggesting pericellular deposition of all key components of the fully developed basement membrane. Immunofluorescence staining of matrix metalloproteinase-2 (MMP-2, 72 kD type IV collagenase, gelatinase A) and MMP-9 (92 kD type IV collagenase, gelatinase B) disclosed only faint staining of MSCs, but MMP-9 was strongly induced during adipogenesis, whereas MSC supernatants disclosed in zymography pro-MMP-2 and faint pro-MMP-9 bands, which increased over time, with partial conversion of pro-MMP-2 to its active 62 kD form. Differentiation was associated with increasing membrane type 1-MMP/MMP-14 and tissue inhibitor of metalloproteinase-2 (TIMP-2) staining, which may enable participation of type IV collagenases in basement membrane remodelling via ternary MT1-MMP/TIMP-2/MMP-2 or -9 complexes, focalizing the fully active enzyme to the cell surface. MMP-9, which increased more in immunofluorescence staining, was perhaps preferentially bound to cell surface and/or remodelling adipocyte basement membrane. These results suggest that upon MSC-adipocyte differentiation collagen type IV synthesis and remodelling become necessary when intracellular accumulation of fat necessitates a dynamically supporting and instructive, partly denatured adipogenic pericellular type IV collagen scaffold. 相似文献
99.
An important issue in conservation planning is to study the distribution and abundance patterns of species in natural landscapes.
Information of concordant and clumped species distribution pattertns can enhance attempts to focus conservation efforts in
sites/areas preferred by various species. We compared bird species abundance, community composition and species distribution
patterns in three large old-growth forest areas (size 40–120 km2) in northern boreal Finland on the basis of quantitative bird censuses. Total bird density and species composition, and mean
density and variances of the most abundant species were highly similar between the three areas. Most of the bird species were
distributed randomly within the areas and species preferring old-growth forests showed compensatory density variation without
preference for any sub-area. Mean density of species preferring old-growth forests was significantly higher in the studied
large old-growth forests than in smaller old-growth forests and was about threefold higher than regional density of species
in a predominantly managed landscape matrix. Bird species preferring old-growth forests are probably not dependent on a certain
specific part of a virgin boreal forest landscape but rather on the overall size of the high-quality and diverse old-growth
forest area. 相似文献
100.
Recent sedimentological conditions in the delta of the river Kyrönjoki,Western Finland 总被引:1,自引:1,他引:0
Heikkilä Raimo 《Hydrobiologia》1986,143(1):371-377
The estuary of the River Kyrönjoki was echo sounded and, on the basis of these results the delta was delimited and areas of erosion and accumulation were separated. Samples of the sediment surface (0–2 cm) from 65 sites in the estuary were analysed for organic content, C, N, P, Ca, Fe, Mn, Pb, Cu, Zn, Cd and Hg. On the basis of the chemical analyses the delta was divided into two parts according to the sedimentary conditions: (I) In the inner part, where acid fresh water of c. pH 5.5 from the river is predominant, the conditions were reducing. The Fe/Mn ratio of the sediment was high. The heavy metal content was usually low. The Hg content in the organic compounds of the sediment was, due to the acidity, higher than in the outer part. (II) In the outer part of the delta, where neutral brackish water of pH c. 7.0 dominates, the sedimentary conditions were mostly oxidizing. The Fe/Mn ratio was very low. The heavy metal and organic content was mostly high in the accumulation areas. This is because the fine-grained allochthonous material, which has a high heavy metal and organic content, flocculates and precipitates when it reaches the brackish water of the Gulf of Bothnia, and the salinity and the pH are higher. 相似文献