全文获取类型
收费全文 | 4082篇 |
免费 | 238篇 |
国内免费 | 2篇 |
出版年
2024年 | 2篇 |
2023年 | 37篇 |
2022年 | 58篇 |
2021年 | 117篇 |
2020年 | 99篇 |
2019年 | 107篇 |
2018年 | 102篇 |
2017年 | 112篇 |
2016年 | 202篇 |
2015年 | 233篇 |
2014年 | 231篇 |
2013年 | 314篇 |
2012年 | 363篇 |
2011年 | 335篇 |
2010年 | 239篇 |
2009年 | 174篇 |
2008年 | 254篇 |
2007年 | 256篇 |
2006年 | 216篇 |
2005年 | 192篇 |
2004年 | 147篇 |
2003年 | 154篇 |
2002年 | 132篇 |
2001年 | 23篇 |
2000年 | 28篇 |
1999年 | 25篇 |
1998年 | 34篇 |
1997年 | 21篇 |
1996年 | 20篇 |
1995年 | 15篇 |
1994年 | 13篇 |
1993年 | 9篇 |
1992年 | 3篇 |
1991年 | 5篇 |
1990年 | 11篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 4篇 |
1983年 | 6篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1980年 | 5篇 |
1979年 | 2篇 |
1977年 | 2篇 |
1975年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有4322条查询结果,搜索用时 31 毫秒
861.
Patrizzia Mastromatteo-Alberga Fabiola Placeres-Uray Marcelo A. Alfonzo-González Ramona Gonzalez de Alfonzo Itala Lippo de Becemberg 《Journal of receptor and signal transduction research》2016,36(3):278-287
Muscarinic antagonists, via muscarinic receptors increase the cAMP/cGMP levels at bovine tracheal smooth muscle (BTSM) through the inhibition of phosphodiesterases (PDEs), displaying a similar behavior of vinpocetine (a specific-PDE1 inhibitor). The presence of PDE1 hydrolyzing both cyclic nucleotides in BTSM strips was revealed. Moreover, a vinpocetine and muscarinic antagonists inhibited PDE1 located at plasma membranes (PM) fractions from BTSM showing such inhibition, an M2AChR pharmacological profile. Therefore, a novel Ca2+/CaM dependent and vinpocetine inhibited PDE1 was purified and characterized at PM fractions from BTSM. This PDE1 activity was removed from PM fractions using a hypotonic buffer and purified some 38 fold using two columns (Q-Sepharose and CaM-agarose). This PDE1 was stimulated by CaM and inhibited by vinpocetine showing two bands in PAGE-SDS (56, 58?kDa) being the 58?kDa identified as PDE1A by Western blotts. This PDE1A activity was assayed with [3H]cGMP and [3H]cAMP exhibiting a higher affinity as Km (μM) for cGMP than cAMP but being close values with Vmax cAMP/cGMP ratio of 1.5. The co-factor Mg2+ showed similar K(A) (mM) for both cyclic nucleotides. Vinpocetine showed similar inhibition concentration 50% (IC50 of 4.9 and 4.6?μM) for cAMP and cGMP, respectively. CaM stimulated the cyclic nucleotides hydrolysis by PDE1A exhibiting similar activation constant as K(CaM), in nM range. The original finding was the identification and purification of a vinpocetine and muscarinic antagonist-inhibited and CaM-activated PM-bound PDE1A, linked to M2AChR. A model of this novel signal transducing cascade for the regulation of cyclic nucleotides levels at BTSM is proposed. 相似文献
862.
863.
Marcelo Hermes-Lima 《Journal of molecular evolution》1990,31(5):353-358
Summary The formation of pyrophosphate (PPi) by condensation of orthophosphate (Pi) at low temperature (37°C) in the absence of condensing or phosphorylating agents could have been an ancient process in chemical evolution. In the present investigation the synthesis of32PPi from32Pi was carried out at pH 8.0 and PPi was found in larger amounts in the presence of insoluble Pi (with calcium or manganese ions) than in its absence (with magnesium ions, or with no divalent cations present). After 10 days of incubation in the presence of precipitated calcium phosphate, about 1.6 nmol/ml of PPi was formed (0.057% yield relative to insoluble Pi). The hypothesis that the reaction is dependent on precipitated Pi was reinforced by the effect of adding dimethyl sulfoxide (2.1–9.9 M) in the presence of magnesium ions: the amount of magnesium phosphate precipitated in the presence of the organic solvent was proportional to the amount of PPi formed. The large and negative activation entropies found in aqueous media with calcium ions and in a medium containing 11.3 M dimethyl sulfoxide with magnesium ions suggest that the reaction was favored by a hydrophobic phenomenon at the surface of solid Pi. This reaction could serve as a model for prebiotic formation of PPi. 相似文献
864.
Rat LINE1: The origin and evolution of a family of long interspersed middle repetitive DNA elements 总被引:3,自引:0,他引:3
Marcelo Bento Soares Eric Schon Argiris Efstratiadis 《Journal of molecular evolution》1985,22(2):117-133
Summary We present approximately 7.0 kb of composite DNA sequence of a long interspersed middle repetitive element (LINE1) present in high copy number in the rat genome. The family of these repeats, which includes transcribing members, is the rat homologue of the mouse MIF-Bam-R and human Kpn I LINEs. Sequence alignments between speciments from these three species define the length of a putative unidentified open reading frame, and document extensive recombination events that, in conjunction with retroposition, have generated this large family of pseudogenes and pseudogene fragments. Comparative mapping of truncated elements indicates that a specific endonucleolytic activity might bei involved in illegitimate (nonhomologous) recombination events. Sequence divergence analyses provide insights into the origin and molecular evolution of these elements. 相似文献
865.
Peptidylarginine deiminase 4 concentration,but not PADI4 polymorphisms,is associated with ICU mortality in septic shock patients
下载免费PDF全文
![点击此处可从《Journal of cellular and molecular medicine》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Nara Aline Costa Ana Lúcia Gut Paula Schmidt Azevedo Bertha Furlan Polegato Eloá Siqueira Magalhães Larissa Lumi Watanabe Ishikawa Rita de Cassia Siqueira Bruder Evelyn Aparecida da Silva Renan Braga Gonçalves Suzana Erico Tanni Marcelo Macedo Rogero Marina Maintinguer Norde Natália Baraldi Cunha Leonardo Antonio Mamede Zornoff Sergio Alberto Rupp de Paiva Marcos Ferreira Minicucci 《Journal of cellular and molecular medicine》2018,22(10):4732-4737
The objective of our study was to evaluate the association between peptidylarginine deiminase 4 (PAD4) concentration and its polymorphisms with mortality in patients with septic shock . We prospectively evaluated 175 patients aged over 18 years with septic shock upon intensive care unit (ICU) admission. However, 48 patients were excluded. Thus, 127 patients were enrolled in the study. At the time of the patients’ enrollment, demographic information was recorded. Blood samples were taken within the first 24 hours of the patient's admission to determine serum PAD4 concentrations and its polymorphism PADI4_89 [rs11203366], PADI4_94 [rs2240340] and PADI4_104 [rs1748033]. The mean age was 63.3 ± 15.2 years, 56.7% were male, PAD4 concentration was 4.62 (2.48‐6.20) ng/mL and the ICU mortality rate was 67.7%. The patients who died in the ICU had higher APACHE II and Sequential Organ Failure Assessment (SOFA) scores. In addition, PAD4 concentration was higher in patients who died during ICU stay. However, there were no differences regarding PADI4 polymorphisms and ICU mortality. In the logistic regression models, PAD4 concentrations were associated with ICU mortality when adjusted for APACHE II score and lactate (OR: 1.477; CI 95%: 1.186‐1.839; P < .001), and when adjusted for age, gender and APACHE II score (OR: 1.392; CI 95%: 1.145‐1.692; P < .001). In conclusion, PAD4 concentration, but not PADI4_89, PADI4_94 and PADI4_104 polymorphisms, is associated with ICU mortality in septic shock patients. 相似文献
866.
867.
Ana Paula Negreiros Nunes Alves Edmar Maciel Lima Júnior Nelson Sarto Piccolo Marcelo José Borges de Miranda Maria Elisa Quezado Lima Verde Antônio Ernando Carlos Ferreira Júnior Paulo Goberlânio de Barros Silva Victor Pinheiro Feitosa Tereza Jesus Pinheiro Gomes de Bandeira Monica Beatriz Mathor Manoel Odorico de Moraes 《Cell and tissue banking》2018,19(3):373-382
Tissue bioengineering development is a global concern and different materials are studied and created to be safe, effective and with low cost. Nile Tilapia skin had shown its biological potential as covers for the burn wound. This study evaluates the tilapia skin histological, collagen properties and tensiometric resistance, after treatment by different sterilization methods. Tilapia skin samples were submitted to two sterilization processes: (1) chemical, which consisted in two 2% chlorhexidin baths, followed by sequential baths in increasing glycerol concentrations; and (2) radiation, when glycerolized skin samples were submitted to gamma radiation at 25, 30 and 50 kGy. Microscopic analyzes were performed through Haematoxylin–eosin and Picrosirius Red under polarized light. For tensiometric analysis, traction tests were performed. Glycerol treated skin presented a discrete collagen fibers disorganization within the deep dermis, while irradiated skin did not show any additional change. Throughout the steps of chemical sterilization, there was a higher proportion of collagen with red/yellow birefringence (type I) in the skin samples up to the first bath in chlorhexidin, when compared to samples after the first two glycerol baths (P < 0.005). However, there was no difference in relation to total collagen between groups. In irradiated skin, there was a larger total collagen preservation when using until 30 kGy (P < 0.005). Tensiometric evaluation did not show significant differences in relation to maximum load in the groups studied. We concluded that chemical and radiation (25 and 30 kGy) are efficient methods to sterilize Nile Tilapia skin without altering its microscopic or tensiometric characteristics. 相似文献
868.
Camila C. B. Brito Fernando V. Maluf Gustavo M. A. de Lima Rafael V. C. Guido Marcelo S. Castilho 《Molecular biotechnology》2018,60(8):595-600
Leishmaniasis is one of the most important neglected tropical diseases, with a broad spectrum of clinical manifestations. Among the clinical manifestations of the disease, cutaneous leishmaniasis, caused by species of Leishmania braziliensis, presents wide distribution in Brazil. In this work, we performed the cloning, expression, and purification of the enzyme superoxide dismutase of Leishmania braziliensis (LbSOD-B2) considered a promising target for the search of new compounds against leishmaniasis. In vitro assays based on pyrogallol oxidation showed that LbSOD-B2 is most active around pH 8 and hydrogen peroxide is a LbSOD-B2 inhibitor at low millimolar range (IC50?=?1 mM). 相似文献
869.
Daiane Cristina F. Golbert Eliane Santana-Van-Vliet Marcelo Ribeiro-Alves Marbella Maria B. da Fonsêca Ailin Lepletier Daniella Arêas Mendes-da-Cruz 《Cell Adhesion & Migration》2018,12(2):152-167
The thymus supports differentiation of T cell precursors. This process requires relocation of developing thymocytes throughout multiple microenvironments of the organ, mainly with thymic epithelial cells (TEC), which control intrathymic T cell differentiation influencing the formation and maintenance of the immunological synapse. In addition to the proteins of the major histocompatibility complex (MHC), this structure is supported by several adhesion molecules. During the process of thymopoiesis, we previously showed that laminin-mediated interactions are involved in the entrance of T-cell precursors into the thymus, as well as migration of differentiating thymocytes within the organ. Using small interference RNA strategy, we knocked-down the ITGA6 gene (which encodes the CD49f integrin α-chain) in cultured human TEC, generating a decrease in the expression of the corresponding CD49f subunit, in addition to modulation in several other genes related to cell adhesion and migration. Thymocyte adhesion to TEC was significantly impaired, comprising both immature and mature thymocyte subsets. Moreover, we found a modulation of the MHC, with a decrease in membrane expression of HLA-ABC, in contrast with increase in the expression of HLA-DR. Interestingly, the knockdown of the B2M gene (encoding the β-2 microglobulin of the HLA-ABC complex) increased CD49f expression levels, thus unraveling the existence of a cross-talk event in the reciprocal control of CD49f and HLA-ABC. Our data suggest that the expression levels of CD49f may be relevant in the general control of MHC expression by TEC and consequently the corresponding synapse with developing thymocytes mediated by the T-cell receptor. 相似文献
870.
Luis?Carlos?MartínezEmail authorView authors OrcID profile
return OK on get Angelica?Plata-Rueda Guilherme?da?Silva Neves Jamile?Fernanda?Cossolin Marcelo?Henrique?dos?Santos José?Cola?Zanuncio José?Eduardo?Serr?o 《Protoplasma》2018,255(6):1693-1702
The osmeterium, found in papilionoid larvae, is an eversible organ with an exocrine gland that produces substances in response to the mechanical disturbances caused by natural enemies. The anatomy, histology and ultrastructure of the osmeterium, and the chemical composition of its secretion in Heraclides thoas (Lepidoptera: Papilionidae) were studied. Heraclides thoas larvae have a Y-shaped osmeterium in the thorax. The surface of the osmeterium has a rough cuticle lining cells with papillae and irregular folds, whereas the cells that limited the gland pores are irregular, folded, and devoid of papillae. Two types of cells are found: (i) cuticular epidermal cells on the surface of the tubular arms of the osmeterium and (ii) secretory cells of the ellipsoid gland within the region of the glandular pore. Cuticular epidermal cells show a thick cuticle, with several layers divided into epicuticle and lamellar endocuticle. Secretory cells are polygonal, with extensive folds in the basal plasma membrane that formed extracellular channels. The cytoplasm has mitochondria, ribosomes, and numerous vacuoles, whereas the nucleus is irregular in shape with decondensed chromatin. The chemical composition of the osmeterial secretion comprised (Z)-α-bisabolene (25.4%), α-bisabol (20.6%), β-bisabolene (13.1%), (E)-α-bisabolene 8%), β-pinene (9.91%), longipinene epoxide (8.92%), (Z)-β-farnesene (6.96%), β-caryophyllene (2.05%), farnesol (1.86%), linalyl propionate (1.86%), and 1-octyn-4-ol (1.07%). The morphological features suggest that the cuticular epidermal cells play a major role in the maintenance and protection of the osmeterium, whereas secretory cells are responsible for production of osmeterial secretions. 相似文献