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91.
Anne Zanchi Luc Tappy Kim-Anne Lê Murielle Bortolotti Nicolas Theumann Georges Halabi Thierry Gauthier Claudine Mathieu Sylvie Tremblay Pauline Coti Bertrand Michel Burnier Daniel Teta 《PloS one》2014,9(10)
Background
Fat redistribution, increased inflammation and insulin resistance are prevalent in non-diabetic subjects treated with maintenance dialysis. The aim of this study was to test whether pioglitazone, a powerful insulin sensitizer, alters body fat distribution and adipokine secretion in these subjects and whether it is associated with improved insulin sensitivity.Trial Design
This was a double blind cross-over study with 16 weeks of pioglitazone 45 mg vs placebo involving 12 subjects.Methods
At the end of each phase, body composition (anthropometric measurements, dual energy X-ray absorptometry (DEXA), abdominal CT), hepatic and muscle insulin sensitivity (2-step hyperinsulinemic euglycemic clamp with 2H2-glucose) were measured and fasting blood adipokines and cardiometabolic risk markers were monitored.Results
Four months treatment with pioglitazone had no effect on total body weight or total fat but decreased the visceral/sub-cutaneous adipose tissue ratio by 16% and decreased the leptin/adiponectin (L/A) ratio from 3.63×10−3 to 0.76×10−3. This was associated with a 20% increase in hepatic insulin sensitivity without changes in muscle insulin sensitivity, a 12% increase in HDL cholesterol and a 50% decrease in CRP.Conclusions/Limitations
Pioglitazone significantly changes the visceral-subcutaneous fat distribution and plasma L/A ratio in non diabetic subjects on maintenance dialysis. This was associated with improved hepatic insulin sensitivity and a reduction of cardio-metabolic risk markers. Whether these effects may improve the outcome of non diabetic end-stage renal disease subjects on maintenance dialysis still needs further evaluation.Trial Registration
ClinicalTrial.gov NCT01253928相似文献92.
The structure and reactivity of a covalently linked catechol-ortho-benzoquinone (hemiquinone) is studied by UV-Vis and IR absorption spectroscopy. Nanosecond transient absorption spectroscopy of the hemiquinone reveals the formation of bi-radical state consisting of two semiquinone units. It is a long-lived state resulting from proton coupled electron transfer (PCET). 相似文献
93.
Rita Casc?o Bruno Vidal Inês P. Lopes Eunice Paisana José Rino Luis F. Moita Jo?o E. Fonseca 《PloS one》2015,10(12)
Background
Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease characterized by cellular infiltration into the joints, hyperproliferation of synovial cells and bone damage. Available treatments for RA only induce remission in around 30% of the patients, have important adverse effects and its use is limited by their high cost. Therefore, compounds that can control arthritis, with an acceptable safety profile and low production costs are still an unmet need. We have shown, in vitro, that celastrol inhibits both IL-1β and TNF, which play an important role in RA, and, in vivo, that celastrol has significant anti-inflammatory properties. Our main goal in this work was to test the effect of celastrol in the number of sublining CD68 macrophages (a biomarker of therapeutic response for novel RA treatments) and on the overall synovial tissue cellularity and joint structure in the adjuvant-induced rat model of arthritis (AIA).Methods
Celastrol was administered to AIA rats both in the early (4 days after disease induction) and late (11 days after disease induction) phases of arthritis development. The inflammatory score, ankle perimeter and body weight were evaluated during treatment period. Rats were sacrificed after 22 days of disease progression and blood, internal organs and paw samples were collected for toxicological blood parameters and serum proinflammatory cytokine quantification, as well as histopathological and immunohistochemical evaluation, respectively.Results
Here we report that celastrol significantly decreases the number of sublining CD68 macrophages and the overall synovial inflammatory cellularity, and halted joint destruction without side effects.Conclusions
Our results validate celastrol as a promising compound for the treatment of arthritis. 相似文献94.
95.
LM de-Oliveira-Pinto CF Marinho TF Povoa EL de Azeredo LA de Souza LD Barbosa AR Motta-Castro AM Alves CA Ávila LJ de Souza RV da Cunha PV Damasco MV Paes CF Kubelka 《PloS one》2012,7(7):e38527
Little is known about the role of chemokines/chemokines receptors on T cells in natural DENV infection. Patients from DENV-2 and -3- outbreaks were studied prospectively during the acute or convalescent phases. Expression of chemokine receptor and activation markers on lymphocyte subpopulations were determined by flow cytometry analysis, plasma chemokine ligands concentrations were measured by ELISA and quantification of CCL5/RANTES(+) cells in liver tissues from fatal dengue cases was performed by immunochemistry. In the acute DENV-infection, T-helper/T-cytotoxic type-1 cell (Th1/Tc1)-related CCR5 is significantly higher expressed on both CD4 and CD8 T cells. The Th1-related CXCR3 is up-regulated among CD4 T cells and Tc2-related CCR4 is up-regulated among CD8 T cells. In the convalescent phase, all chemokine receptor or chemokine ligand expression tends to reestablish control healthy levels. Increased CCL2/MCP-1 and CCL4/MIP-1β but decreased CCL5/RANTES levels were observed in DENV-patients during acute infection. Moreover, we showed an increased CD107a expression on CCR5 or CXCR3-expressing T cells and higher expression of CD29, CD44(HIGH) and CD127(LOW) markers on CCR4-expressing CD8 T cells in DENV-patients when compared to controls. Finally, liver from dengue fatal patients showed increased number of cells expressing CCL5/RANTES in three out of four cases compared to three death from a non-dengue patient. In conclusion, both Th1-related CCR5 and CXCR3 among CD4 T cells have a potential ability to exert cytotoxicity function. Moreover, Tc1-related CCR5 and Tc2-related CCR4 among CD8 T cells have a potential ability to exert effector function and migration based on cell markers evaluated. The CCR5 expression would be promoting an enhanced T cell recruitment into liver, a hypothesis that is corroborated by the CCL5/RANTES increase detected in hepatic tissue from dengue fatal cases. The balance between protective and pathogenic immune response mediated by chemokines during dengue fever will be discussed. 相似文献
96.
Soares JB Pimentel-Nunes P Afonso L Rolanda C Lopes P Roncon-Albuquerque R Gonçalves N Boal-Carvalho I Pardal F Lopes S Macedo G Lara-Santos L Henrique R Moreira-Dias L Gonçalves R Dinis-Ribeiro M Leite-Moreira AF 《Innate immunity》2012,18(5):700-708
We evaluated expression of TLR2, TLR4 and proinflammatory genes [NF-κB, TNF-α, cyclooxygenase-2 (COX-2)] in liver samples of patients in different stages of liver disease. Fifteen patients with unexplained transaminases elevation (reference group), 22 with viral chronic hepatitis (hepatitis group), 14 with virus-induced severe fibrosis/cirrhosis (cirrhosis group) and 10 with hepatocarcinoma (hepatocarcinoma group) were consecutively included in the study. Quantification of TLR2, TLR4, NF-κB, TNF-α and COX-2 mRNA was done by real-time RT-PCR and TLR2 and TLR4 protein expression was evaluated by immunohistochemistry. Compared with reference, TLR2 and TLR4 mRNA was increased in hepatitis (TLR2: 2.66?±?0.69; TLR4: 3.11?±?0.79; P?0.05) and cirrhosis (TLR2: 2.14?±?0.5; TLR4: 1.74?±?0.27; P?0.05) and decreased in hepatocarcinoma (TLR2: 0.48?±?0.15; TLR4: 0.54?±?0.10; P?0.05). This associated with increased TNF-α and COX-2 mRNA in hepatitis (TNF-α: 3.24?±?0.79; COX-2: 2.47?±?0.36; P?0.05) and cirrhosis (TNF-α: 1.73?±?0.28; COX-2: 1.8?±?0.35, P?0.05), whereas NF-κB mRNA was increased in hepatitis (2.42?±?0.31; P?0.05) and unchanged in cirrhosis (1.34?±?0.17; P?=?0.3). Hepatocarcinoma presented increased COX-2 mRNA (1.63?±?0.15; P?0.05) and maintained (at decreased levels) mRNA of NF-κB (0.52?±?0.12) and TNF-α (0.52?±?0.12; P?0.05, all genes). Immunohistochemistry confirmed increased expression of TLR2 and TLR4 in hepatitis and cirrhosis and maintained expression in hepatocarcinoma. Upregulation of TLR2, TLR4 and their proinflammatory mediators is associated with virus-induced hepatic IFC sequence. 相似文献
97.
Z Carvalho-Santos P Machado I Alvarez-Martins SM Gouveia SC Jana P Duarte T Amado P Branco MC Freitas ST Silva C Antony TM Bandeiras M Bettencourt-Dias 《Developmental cell》2012,23(2):412-424
Cilia and flagella are involved in a variety of processes and human diseases, including ciliopathies and sterility. Their motility is often controlled by?a central microtubule (MT) pair localized within the ciliary MT-based skeleton, the axoneme. We characterized the formation of the motility apparatus in detail in Drosophila spermatogenesis. We show that assembly of the central MT pair starts prior to the meiotic divisions, with nucleation of a singlet MT within the basal body of a small cilium, and that the second MT of the pair only assembles much later, upon flagella formation. BLD10/CEP135, a conserved player in centriole and flagella biogenesis, can bind and stabilize MTs and is required for the early steps of central MT pair formation. This work describes a genetically tractable system to study motile cilia formation and provides an explanation for BLD10/CEP135's role in assembling highly stable MT-based structures, such as motile axonemes and centrioles. 相似文献
98.
Ivo H. J. Ploemen Miguel Prudêncio Bruno G. Douradinha Jai Ramesar Jannik Fonager Geert-Jan van Gemert Adrian J. F. Luty Cornelus C. Hermsen Robert W. Sauerwein Fernanda G. Baptista Maria M. Mota Andrew P. Waters Ivo Que Clemens W. G. M. Lowik Shahid M. Khan Chris J. Janse Blandine M. D. Franke-Fayard 《PloS one》2009,4(11)
The quantitative analysis of Plasmodium development in the liver in laboratory animals in cultured cells is hampered by low parasite infection rates and the complicated methods required to monitor intracellular development. As a consequence, this important phase of the parasite''s life cycle has been poorly studied compared to blood stages, for example in screening anti-malarial drugs. Here we report the use of a transgenic P. berghei parasite, PbGFP-Luccon, expressing the bioluminescent reporter protein luciferase to visualize and quantify parasite development in liver cells both in culture and in live mice using real-time luminescence imaging. The reporter-parasite based quantification in cultured hepatocytes by real-time imaging or using a microplate reader correlates very well with established quantitative RT-PCR methods. For the first time the liver stage of Plasmodium is visualized in whole bodies of live mice and we were able to discriminate as few as 1–5 infected hepatocytes per liver in mice using 2D-imaging and to identify individual infected hepatocytes by 3D-imaging. The analysis of liver infections by whole body imaging shows a good correlation with quantitative RT-PCR analysis of extracted livers. The luminescence-based analysis of the effects of various drugs on in vitro hepatocyte infection shows that this method can effectively be used for in vitro screening of compounds targeting Plasmodium liver stages. Furthermore, by analysing the effect of primaquine and tafenoquine in vivo we demonstrate the applicability of real time imaging to assess parasite drug sensitivity in the liver. The simplicity and speed of quantitative analysis of liver-stage development by real-time imaging compared to the PCR methodologies, as well as the possibility to analyse liver development in live mice without surgery, opens up new possibilities for research on Plasmodium liver infections and for validating the effect of drugs and vaccines on the liver stage of Plasmodium. 相似文献
99.
Guilherme Augusto Peres Silva Salvador Alejandro Gezan Melissa Pisaroglo de Carvalho Lígia Regina Lima Gouvêa Cecília Khusala Verardi André Luis Bombonato de Oliveira Paulo de Souza Gonçalves 《Tree Genetics & Genomes》2014,10(6):1511-1518
Rubber tree breeding programs are mainly driven by selection of individuals with high yield and quality of rubber. Data from 51 open-pollinated progenies tested on six sites in Brazil were analyzed over several traits to estimate the following: genetic parameters such as narrow-sense heritability and additive genetic variance in single- and multi-site analyses, type B correlations to determine the relevance of genotype-by-environment interactions and its effects on alternative selection strategies, additive genetic repeatability correlation for rubber yield based on three consecutive yearly measurements, and type A correlations to evaluate trait-to-trait genetic associations for all measured traits. Average rubber yield (RYm) showed an estimated narrow-sense heritability of 0.31, with an estimated type B correlation of 0.84, indicating low levels of genotype-by-environment interaction. The trait survival and number of latex vessel rings (RG) showed larger genotype-by-environment interaction and the lowest heritabilites. High to moderate type B correlation was found for most traits, with a value of 0.85 between diameter (or girth) and RYm; therefore, it is possible to achieve interesting rubber yield genetic gains (over 3 years of measurements) from indirect selection based on diameter at age 2. 相似文献
100.