全文获取类型
收费全文 | 2110篇 |
免费 | 163篇 |
出版年
2023年 | 8篇 |
2022年 | 25篇 |
2021年 | 43篇 |
2020年 | 26篇 |
2019年 | 34篇 |
2018年 | 55篇 |
2017年 | 46篇 |
2016年 | 62篇 |
2015年 | 104篇 |
2014年 | 103篇 |
2013年 | 166篇 |
2012年 | 157篇 |
2011年 | 145篇 |
2010年 | 110篇 |
2009年 | 79篇 |
2008年 | 140篇 |
2007年 | 107篇 |
2006年 | 111篇 |
2005年 | 106篇 |
2004年 | 76篇 |
2003年 | 78篇 |
2002年 | 70篇 |
2001年 | 27篇 |
2000年 | 30篇 |
1999年 | 23篇 |
1998年 | 20篇 |
1997年 | 17篇 |
1996年 | 17篇 |
1995年 | 18篇 |
1994年 | 12篇 |
1993年 | 13篇 |
1992年 | 21篇 |
1991年 | 21篇 |
1990年 | 14篇 |
1989年 | 12篇 |
1988年 | 15篇 |
1987年 | 11篇 |
1986年 | 10篇 |
1985年 | 16篇 |
1984年 | 11篇 |
1983年 | 9篇 |
1982年 | 7篇 |
1981年 | 10篇 |
1980年 | 7篇 |
1979年 | 6篇 |
1975年 | 9篇 |
1974年 | 12篇 |
1968年 | 10篇 |
1966年 | 5篇 |
1964年 | 6篇 |
排序方式: 共有2273条查询结果,搜索用时 31 毫秒
1.
Effects of choline deficiency on rat hepatocytes 总被引:6,自引:0,他引:6
B Lombardi 《Federation proceedings》1971,30(1):139-142
2.
Susanne Berglund Bryan J. Egner Henrik Gradén Joakim Gradén David G.A. Morgan Tord Inghardt Fabrizio Giordanetto 《Bioorganic & medicinal chemistry letters》2009,19(15):4268-4273
Herein, we disclose the discovery and optimization of 2-piperidin-4-yl-acetamide derivatives as MCH-R1 antagonists. Structural investigation of piperidin-4-yl-amide and piperidin-4-yl-ureas identified 2-piperidin-4-yl-acetamide-based MCH-R1 antagonists with outstanding in vivo efficacy but flawed with high affinity towards the hERG potassium channel. While existing hERG SAR information was employed to discover highly potent MCH-R1 antagonists with minimized hERG inhibition, additional hurdles prevented their subsequent clinical exploration. 相似文献
3.
Chiara Pavanello Alice Ossoli Arianna Strazzella Patrizia Risè Fabrizio Veglia Marie Lhomme Paolo Parini Laura Calabresi 《Journal of lipid research》2022,63(7):100232
Mutations in the LCAT gene cause familial LCAT deficiency (Online Mendelian Inheritance in Man ID: #245900), a very rare metabolic disorder. LCAT is the only enzyme able to esterify cholesterol in plasma, whereas sterol O-acyltransferases 1 and 2 are the enzymes esterifying cellular cholesterol in cells. Despite the complete lack of LCAT activity, patients with familial LCAT deficiency exhibit circulating cholesteryl esters (CEs) in apoB-containing lipoproteins. To analyze the origin of these CEs, we investigated 24 carriers of LCAT deficiency in this observational study. We found that CE plasma levels were significantly reduced and highly variable among carriers of two mutant LCAT alleles (22.5 [4.0–37.8] mg/dl) and slightly reduced in heterozygotes (218 [153–234] mg/dl). FA distribution in CE (CEFA) was evaluated in whole plasma and VLDL in a subgroup of the enrolled subjects. We found enrichment of C16:0, C18:0, and C18:1 species and a depletion in C18:2 and C20:4 species in the plasma of carriers of two mutant LCAT alleles. No changes were observed in heterozygotes. Furthermore, plasma triglyceride-FA distribution was remarkably similar between carriers of LCAT deficiency and controls. CEFA distribution in VLDL essentially recapitulated that of plasma, being mainly enriched in C16:0 and C18:1, while depleted in C18:2 and C20:4. Finally, after fat loading, chylomicrons of carriers of two mutant LCAT alleles showed CEs containing mainly saturated FAs. This study of CEFA composition in a large cohort of carriers of LCAT deficiency shows that in the absence of LCAT-derived CEs, CEs present in apoB-containing lipoproteins are derived from hepatic and intestinal sterol O-acyltransferase 2. 相似文献
4.
Chiara D'Onofrio Caterina D. Pesce Tecla Fontana Fabrizio Ciprani Enzo Bonmassar Raffaele Calio 《Cancer immunology, immunotherapy : CII》1990,31(4):213-220
Summary Infection with human T-cell leukemia virus type I (HTLV-I) is associated in vitro and in vivo with a remarkable depression of cell-mediated immune functions. In the present report it is shown that early events following virus-induced suppression of the cell-mediated immune response of freshly isolated cord blood mononuclear cells (CBL) infected with HTLV-I can be partially counteracted by treatment with interferons , or (IFN). All three types of IFN exerted a protective effect on CBL cultures exposed to the virus. This resulted in: (a) a reduced number of virus-positive cells until 4 weeks of culture; (b) delay in the clonal expansion of infected cells (IFN and ); (c) increased natural killer cell activity of CBL, 1 week post-infection (p.i.), mediated by IFN; (d) increase of allospecific recognition of infecting and priming HTLV-I donor MT-2 cells by CBL in a cytotoxic-T-lymphocyte-like response, mediated by IFN and particularly by IFN; (e) phenotype distribution of CBL subpopulations, tested 4 days p.i., more similar to that of non-infected CBL cultures.In contrast, the overall CBL proliferation, that is profoundly depressed during the first week p.i., was not restored by IFN treatments, suggesting that boosting of the cell-mediated killing induced by IFN might involve the maturation of undifferentiated precursor cells rather than stimulation of their proliferation. The improvement of the efficiency of the antiviral immune response induced by treatment with IFN is likely to contribute to the clearance of virus-positive cells during the early phase of infection. This would provide experimental evidence to support an immunopharmacological approach contributing to the conversion of HTLV-I carriers from positive to negative. 相似文献
5.
V Lombardi F Capuano A Coci T R Broun R Graham 《Nauchnye doklady vysshe? shkoly. Biologicheskie nauki》1990,(6):51-60
Physiological and biochemical processes which take place in the nervous system at stroke and neurotrauma are reviewed, and the experience of using low doses of steroid derivatives with piridamole in the treatment of central nervous system (CNS) disorders is summarized. ATPases (including Na,K-ATPase) are reported to play an important role in CNS functioning, the correlation between Na,K-ATPase activity and the extent of CNS injury is revealed. The use of NMR-spectroscopy method for investigation of brain and spinal cord condition in vivo is suggested. 相似文献
6.
7.
Summary The presence of house dust mites and storage mites in dumpsters was investigated in 3 different areas of Venice hinterland. The aim of this study was to find a relationship between some reported respiratory symptoms among 6 workers who were responsible for moving the dumpsters to the truck and the bio-aerosol released from such operation. These symptoms were closely related to the work and after allergological evaluation we found sensitisation to house dust mites in all 6 employees. The mine exposure in the workplace was assessed by a standardized sampling and analysis of dust obtained after brushing the inside surfaces of dumpsters. In 50% of the specimens (10/20) we found mites belonging to the following families: Pyroglyphidae (Dermatophagoides spp.), Acaridae (Acarus siro) and a lower amount of Cheyletidae (Cheyletus spp.). An indirect test (guanine test) was also performed and gave positivity in 16 dust samples (80%). The insides of dumpsters showed to be an optimal environment for mites survival and reproduction because of cracks and grooves on the walls, the high humidity level and the presence of mould. These mites probably come from dwelling places and other environments (markets, slaughters-houses, farms, etc.). This suggests that mites allergens can be released during rubbish discharging from the dumpsters and represent a possible risk for the employees. 相似文献
8.
Fabrizio Arigoni P. Alexandre Kaminski Hauke Hennecke Claudine Elmerich 《Molecular & general genetics : MGG》1991,225(3):514-520
Summary The nucleotide sequence of a 4.1 kb DNA fragment containing the fixABC region of Azorhizobium caulinodans was established. The three gene products were very similar to the corresponding polypeptides of Rhizobium meliloti. The C-terminal domains of both fixB products displayed a high degree of similarity with the -subunits of rat and human electron transfer flavoproteins, suggesting a role for the FixB protein in a redox reaction. Two open reading frames (ORF) were found downstream of fixC. The first ORF was identified as fixX on the basis of sequence homology with fixX from several Rhizobium and Bradyrhizobium strains. The second ORF potentially encoded a 69 amino acid product and was found to be homologous to a DNA region in the Rhodobacter capsulatus nif cluster I. Insertion mutagenesis of the A. caulinodans fixX gene conferred a Nif– phenotype to bacteria grown in the free-living state and a Fix– phenotype in symbiotic association with the host plant Sesbania rostrata. A crude extract from the fixX mutant had no nitrogenase activity. Furthermore, data presented in this paper also indicate that the previously identified nifO gene located upstream of fixA was probably a homologue of the nifW gene of Klebsiella pneumoniae and Azotobacter vinelandii. 相似文献
9.
Tyrosine mutations within the alpha platelet-derived growth factor receptor kinase insert domain abrogate receptor-associated phosphatidylinositol-3 kinase activity without affecting mitogenic or chemotactic signal transduction. 总被引:18,自引:10,他引:8
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
J C Yu M A Heidaran J H Pierce J S Gutkind D Lombardi M Ruggiero S A Aaronson 《Molecular and cellular biology》1991,11(7):3780-3785
A phosphatidylinositol-3 (PI-3) kinase activity of unknown biological function associates with tyrosine kinase-containing proteins, including a number of growth factor receptors after ligand stimulation. In the beta platelet-derived growth factor (beta PDGF) receptor, phosphorylation of a specific tyrosine residue within the kinase insert domain was required for its interaction with this enzyme. We show that substitutions of phenylalanine for tyrosine residue 731 or 742 within the kinase insert domain of the alpha PDGF receptor do not impair PDGF-induced tyrosine phosphorylation of the receptor or of an in vivo substrate, phospholipase C-gamma. Moreover, phosphatidylinositol turnover in response to ligand stimulation is unaffected. However, both lesions markedly impair receptor association with PI-3 kinase. Antiphosphotyrosine antibody-recoverable PI-3 kinase was also dramatically reduced in PDGF-stimulated cells expressing either mutant receptor. Since neither mutation abolished PDGF-induced mitogenesis or chemotaxis, we conclude that alpha PDGF receptor-associated PI-3 kinase activity is not required for either of these major PDGF signalling functions. 相似文献
10.
Conclusive diagnosis of hepatic and pancreatic malignancies by fine needle aspiration 总被引:1,自引:0,他引:1
A study of the diagnosis of hepatic and pancreatic malignancies by fine needle aspiration (FNA) was made, based on 221 aspirates obtained from 209 patients with histologic or clinical confirmation: 159 with hepatic and 50 with pancreatic lesions. The values of sensitivity, specificity and predictivity for positive FNA results were, respectively, 0.84, 0.96 and 1.0 for the liver and 0.76, 1.0 and 1.0 for the pancreas. The composition of the case material showed an incidence of malignant tumors of the liver and pancreas of 84% and 60%, respectively (among which the primary malignancies were 39% and 48%), while nonneoplastic lesions had incidences of 14% and 40%. However, conclusive FNA diagnoses of the histologic type of the primary and the site of origin of metastatic tumors were made in 60% of the hepatic lesions but in only 9% of the pancreatic lesions. Primary hepatocellular carcinoma was diagnosed by FNA of the liver in 95% of the cases; FNA specifically diagnosed 42% of intrahepatic bile duct carcinomas and 40% of hepatic metastases. These findings correlate with the unique cytologic features of primary hepatocellular carcinoma of intrahepatic rather nonspecific morphology of carcinoma of intrahepatic and extrahepatic origin, as well as of pancreatic ductal origin. 相似文献