全文获取类型
收费全文 | 444篇 |
免费 | 28篇 |
专业分类
472篇 |
出版年
2023年 | 1篇 |
2022年 | 10篇 |
2021年 | 6篇 |
2020年 | 5篇 |
2019年 | 6篇 |
2018年 | 13篇 |
2017年 | 8篇 |
2016年 | 12篇 |
2015年 | 32篇 |
2014年 | 32篇 |
2013年 | 33篇 |
2012年 | 31篇 |
2011年 | 43篇 |
2010年 | 26篇 |
2009年 | 23篇 |
2008年 | 21篇 |
2007年 | 26篇 |
2006年 | 29篇 |
2005年 | 18篇 |
2004年 | 16篇 |
2003年 | 12篇 |
2002年 | 9篇 |
2001年 | 7篇 |
2000年 | 7篇 |
1999年 | 5篇 |
1998年 | 1篇 |
1997年 | 4篇 |
1995年 | 4篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有472条查询结果,搜索用时 15 毫秒
31.
De Miguel MP Fuentes-Julián S Blázquez-Martínez A Pascual CY Aller MA Arias J Arnalich-Montiel F 《Current molecular medicine》2012,12(5):574-591
Mesenchymal stem cells (MSCs) have been isolated from a variety of tissues, such as bone marrow, skeletal muscle, dental pulp, bone, umbilical cord and adipose tissue. MSCs are used in regenerative medicine mainly based on their capacity to differentiate into specific cell types and also as bioreactors of soluble factors that will promote tissue regeneration from the damaged tissue cellular progenitors. In addition to these regenerative properties, MSCs hold an immunoregulatory capacity, and elicit immunosuppressive effects in a number of situations. Not only are they immunoprivileged cells, due to the low expression of class II Major Histocompatibilty Complex (MHC-II) and costimulatory molecules in their cell surface, but they also interfere with different pathways of the immune response by means of direct cell-to-cell interactions and soluble factor secretion. In vitro, MSCs inhibit cell proliferation of T cells, B-cells, natural killer cells (NK) and dendritic cells (DC), producing what is known as division arrest anergy. Moreover, MSCs can stop a variety of immune cell functions: cytokine secretion and cytotoxicity of T and NK cells; B cell maturation and antibody secretion; DC maturation and activation; as well as antigen presentation. It is thought that MSCs need to be activated to exert their immunomodulation skills. In this scenario, an inflammatory environment seems to be necessary to promote their effect and some inflammation-related molecules such as tumor necrosis factor-α and interferon-γ might be implicated. It has been observed that MSCs recruit T-regulatory lymphocytes (Tregs) to both lymphoid organs and graft. There is great controversy concerning the mechanisms and molecules involved in the immunosuppressive effect of MSCs. Prostaglandin E2, transforming growth factor-β, interleukins- 6 and 10, human leukocyte antigen-G5, matrix metalloproteinases, indoleamine-2,3-dioxygenase and nitric oxide are all candidates under investigation. In vivo studies have shown many discrepancies regarding the immunomodulatory properties of MSCs. These studies have been designed to test the efficacy of MSC therapy in two different immune settings: the prevention or treatment of allograft rejection episodes, and the ability to suppress abnormal immune response in autoimmune and inflammatory diseases. Preclinical studies have been conducted in rodents, rabbits and baboon monkeys among others for bone marrow, skin, heart, and corneal transplantation, graft versus host disease, hepatic and renal failure, lung injury, multiple sclerosis, rheumatoid arthritis, diabetes and lupus diseases. Preliminary results from some of these studies have led to human clinical trials that are currently being carried out. These include treatment of autoimmune diseases such as Crohn's disease, ulcerative colitis, multiple sclerosis and type 1 diabetes mellitus; prevention of allograft rejection and enhancement of the survival of bone marrow and kidney grafts; and treatment of resistant graft versus host disease. We will try to shed light on all these studies, and analyze why the results are so contradictory. 相似文献
32.
Vanessa González-Ortiz Luis G. Egea Rocio Jiménez-Ramos Francisco Moreno-Marín José L. Pérez-Lloréns Tjeed J. Bouma Fernando G. Brun 《PloS one》2014,9(8)
Seagrass shoots interact with hydrodynamic forces and thereby a positively or negatively influence the survival of associated species. The modification of these forces indirectly alters the physical transport and flux of edible particles within seagrass meadows, which will influence the growth and survivorship of associated filter-feeding organisms. The present work contributes to gaining insight into the mechanisms controlling the availability of resources for filter feeders inhabiting seagrass canopies, both from physical (influenced by seagrass density and patchiness) and biological (regulated by filter feeder density) perspectives. A factorial experiment was conducted in a large racetrack flume, which combined changes in hydrodynamic conditions, chlorophyll a concentration in the water and food intake rate (FIR) in a model active filter-feeding organism (the cockle). Results showed that seagrass density and patchiness modified both hydrodynamic forces and availability of resources for filter feeders. Chlorophyll a water content decreased to 50% of the initial value when densities of both seagrass shoots and cockles were high. Also, filter feeder density controlled resource availability within seagrass patches, depending on its spatial position within the racetrack flume. Under high density of filter-feeding organisms, chlorophyll a levels were lower between patches. This suggests that the pumping activity of cockles (i.e. biomixing) is an emergent key factor affecting both resource availability and FIR for filter feeders in dense canopies. Applying our results to natural conditions, we suggest the existence of a direct correlation between habitat complexity (i.e. shoot density and degree of patchiness) and filter feeders density. Fragmented and low-density patches seem to offer both greater protection from hydrodynamic forces and higher resource availability. In denser patches, however, resources are allocated mostly within the canopy, which would benefit filter feeders if they occurred at low densities, but would be limiting when filter feeder were at high densities. 相似文献
33.
Peroni CN Cecchi CR Damiani R Soares CR Ribela MT do Rocio Arkaten R Bartolini P 《Molecular biotechnology》2006,34(2):239-245
A gene therapy clinical trial for treatment of growth hormone (GH) deficiency has not been reached yet, but several strategies
using different gene transfer methodologies and animal models have been developed and showed successful results. We have set
up an ex vivo gene therapy protocol using primary human keratinocytes transduced with an efficient retroviral vector (LXSN)
encoding the human (hGH) or mouse GH (mGH) genes. These stably modified cells presented high in vitro expression levels of
hGH (7 μg/106 cells/d) and mGH (11 μg/106 cells/d) after selection with geneticin. When the hGH-secreting keratinocytes were grafted onto immunodeficient dwarf mice
(lit/scid), hGH levels in the circulation were about 0.2–0.3 ng/mL during a 12-d assay and these animals presented a significant body
weight increase (p<0.01) compared to the control. Substitution of conventional grafting methodologies with organotypic raft cultures revealed
a peak value of up to 20 ng mGH/mL in the circulation of grafted lit/scid mice at 1 h postimplantation, followed by a rapid decline to baseline (≈2 ng/mL) within 24 h. One week after grafting, however,
the cultured excised implants still presented approx 45% of their original in vitro secretion efficiency. Further studies
are being carrier out to identify the main factor(s) that still constitute one of the major impediments to the success of
this promising model of cutaneous gene therapy. 相似文献
34.
35.
Jacques Simard Rocio Sanchez Francine Durocher Eric Rhaume Carl Turgeon Yvan Labrie Van Luu-The Farida Mebarki Yves Morel Yvan de Launoit Fernand Labrie 《The Journal of steroid biochemistry and molecular biology》1995,55(5-6):489-505
The isoenzymes of the 3β-hydroxysteroid dehydrogenase/5-ene-4-ene-isomerase (3β-HSD) gene family catalyse the transformation of all 5-ene-3β-hydroxysteroids into the corresponding 4-ene-3-keto-steroids and are responsible for the interconversion of 3β-hydroxy- and 3-keto-5-androstane steroids. The two human 3β-HSD genes and the three related pseudogenes are located on the chromosome 1p13.1 region, close to the centromeric marker D1Z5. The 3β-HSD isoenzymes prefer NAD+ to NADP+ as cofactor with the exception of the rat liver type III and mouse kidney type IV, which both prefer NADPH as cofactor for their specific 3-ketosteroid reductase activity due to the presence of Tyr36 in the rat type III and of Phe36 in mouse type IV enzymes instead of Asp36 found in other 3β-HSD isoenzymes. The rat types I and IV, bovine and guinea pig 3β-HSD proteins possess an intrinsic 17β-HSD activity psecific to 5-androstane 17β-ol steroids, thus suggesting that such “secondary” activity is specifically responsible for controlling the bioavailability of the active androgen DHT. To elucidate the molecular basis of classical form of 3β-HSD deficiency, the structures of the types I and II 3β-HSD genes in 12 male pseudohermaphrodite 3β-HSD deficient patients as well as in four female patients were analyzed. The 14 different point mutations characterized were all detected in the type II 3β-HSD gene, which is the gene predominantly expressed in the adrenals and gonads, while no mutation was detected in the type I 3β-HSD gene predominantly expressed in the placenta and peripheral tissues. The mutant type II 3β-HSD enzymes carrying mutations detected in patients affected by the salt-losing form exhibit no detectable activity in intact transfected cells, at the exception of L108W and P186L proteins, which have some residual activity (1%). Mutations found in nonsalt-loser patients have some residual activity ranging from 1 to 10% compared to the wild-type enzyme. Characterization of mutant proteins provides unique information on the structure-function relationships of the 3β-HSD superfamily. 相似文献
36.
Julio Alfonso Cruz Medina Jessica Enriquez Farias Andrés Cruz Hernández Rocio Garcia Martinez Sara Solis Valdes Gilberto Hernandez Silva 《Geomicrobiology journal》2013,30(5):454-461
Metal phytoextraction assisted by bacteria plays an important role in bioremediation systems. In this work, mercury-resistant bacterial strains were isolated from soils with high levels of mercury (San Joaquin, Queretaro State, Mexico) and identified as Bacillus sp. based on the 16S rDNA gene sequence analysis. The bacterial strains were found to exhibit different multiple mercury-resistance and carbon source utilization characteristics. The mercury reduction ability was tested through a volatilization assay. The bacterial isolates were also evaluated for their ability to promote growth and mercury uptake in tomato plants. In a roll towel assay, the maximum vigor index of tomato plants was obtained with the inoculation of Bacillus sp. A2, A12, B11, B15 and C1, while in a pot assay, the maximum vigor index was obtained with the inoculation of Bacillus sp. A6, A7 and B20, compared with un-inoculated controls in the presence of HgCl2. Maximum Hg accumulation in the roots and shoots of tomato plants was obtained only with Bacillus sp. A7 in the roll towel assay, whereas in the pot assay, maximum accumulation was obtained with Bacillus sp. A12 compared with un-inoculated controls. Our results show that mercury accumulation in tissue is enhanced by these plant growth promoting bacterial strains, which recommends their possible use as microbe-assisted phytoremediation systems in mercury-polluted soils. 相似文献
37.
Dana B. Hancock Isabelle Romieu Min Shi Juan-Jose Sienra-Monge Hao Wu Grace Y. Chiu Huiling Li Blanca Estela del Rio-Navarro Saffron A. G. Willis-Owens Scott T. Weiss Benjamin A. Raby Hong Gao Celeste Eng Rocio Chapela Esteban G. Burchard Hua Tang Patrick F. Sullivan Stephanie J. London 《PLoS genetics》2009,5(8)
Many candidate genes have been studied for asthma, but replication has varied. Novel candidate genes have been identified for various complex diseases using genome-wide association studies (GWASs). We conducted a GWAS in 492 Mexican children with asthma, predominantly atopic by skin prick test, and their parents using the Illumina HumanHap 550 K BeadChip to identify novel genetic variation for childhood asthma. The 520,767 autosomal single nucleotide polymorphisms (SNPs) passing quality control were tested for association with childhood asthma using log-linear regression with a log-additive risk model. Eleven of the most significantly associated GWAS SNPs were tested for replication in an independent study of 177 Mexican case–parent trios with childhood-onset asthma and atopy using log-linear analysis. The chromosome 9q21.31 SNP rs2378383 (p = 7.10×10−6 in the GWAS), located upstream of transducin-like enhancer of split 4 (TLE4), gave a p-value of 0.03 and the same direction and magnitude of association in the replication study (combined p = 6.79×10−7). Ancestry analysis on chromosome 9q supported an inverse association between the rs2378383 minor allele (G) and childhood asthma. This work identifies chromosome 9q21.31 as a novel susceptibility locus for childhood asthma in Mexicans. Further, analysis of genome-wide expression data in 51 human tissues from the Novartis Research Foundation showed that median GWAS significance levels for SNPs in genes expressed in the lung differed most significantly from genes not expressed in the lung when compared to 50 other tissues, supporting the biological plausibility of our overall GWAS findings and the multigenic etiology of childhood asthma. 相似文献
38.
María-Angeles Aller Jorge-Luis Arias Arturo Cruz Jaime Arias 《Theoretical biology & medical modelling》2007,4(1):1-25
Background
Portal hypertension is a clinical syndrome that manifests as ascites, portosystemic encephalopathy and variceal hemorrhage, and these alterations often lead to death.Hypothesis
Splanchnic and/or systemic responses to portal hypertension could have pathophysiological mechanisms similar to those involved in the post-traumatic inflammatory response. The splanchnic and systemic impairments produced throughout the evolution of experimental prehepatic portal hypertension could be considered to have an inflammatory origin. In portal vein ligated rats, portal hypertensive enteropathy, hepatic steatosis and portal hypertensive encephalopathy show phenotypes during their development that can be considered inflammatory, such as: ischemia-reperfusion (vasodilatory response), infiltration by inflammatory cells (mast cells) and bacteria (intestinal translocation of endotoxins and bacteria) and lastly, angiogenesis. Similar inflammatory phenotypes, worsened by chronic liver disease (with anti-oxidant and anti-enzymatic ability reduction) characterize the evolution of portal hypertension and its complications (hepatorenal syndrome, ascites and esophageal variceal hemorrhage) in humans.Conclusion
Low-grade inflammation, related to prehepatic portal hypertension, switches to high-grade inflammation with the development of severe and life-threatening complications when associated with chronic liver disease. 相似文献39.
Larissa Rosa de OLIVEIRA Rocio LOIZAGA DE CASTRO Susana CÁRDENAS‐ALAYZA Sandro Luis BONATTO 《Mammal Review》2012,42(4):275-303
- 1 Most aquatic mammals have high dispersal potential, and there are often severe conservation concerns related to their legal or illegal harvesting. Therefore, economic, social and forensic factors often arise in decisions relating to their population management. Molecular markers are essential tools in modern conservation genetics, revealing previously unknown aspects of aquatic mammal behaviour, natural history, population structure and demography. Molecular markers also have been used to define management units, to recognize taxonomic units, to conduct forensic analyses and to control illegal wildlife trade, providing valuable information for decision‐making in wildlife conservation and management.
- 2 We review studies published in peer‐reviewed journals between 1993 and 2010, in which genetic approaches have been applied to conservation‐related issues involving natural populations of 25 species of aquatic mammals in South America. These studies cover just 34% of the 70 aquatic mammal species recorded in South America.
- 3 Most of the studies are related to population structure, phylogeography, gene flow and dispersal movements. In addition, recent findings relate to evolutionarily significant units, management units, forensics and conservation policy.
- 4 Finally, we look to the future and, based on numbers of studies and conservation concerns, suggest which species, geographic areas and genetic studies should be prioritized. Moreover, we discuss constraints on research and suggest collaborative works that would provide critical information towards the effective conservation and management of aquatic mammals in South America.
40.
Mercedes Romero-Gámez Assumpció Antón Rocio Leyva Elisa M. Suárez-Rey 《The International Journal of Life Cycle Assessment》2017,22(5):798-811