全文获取类型
收费全文 | 1003篇 |
免费 | 52篇 |
国内免费 | 2篇 |
学科分类
医药卫生 | 1057篇 |
出版年
2023年 | 8篇 |
2022年 | 9篇 |
2021年 | 20篇 |
2020年 | 18篇 |
2019年 | 26篇 |
2018年 | 27篇 |
2017年 | 21篇 |
2016年 | 20篇 |
2015年 | 20篇 |
2014年 | 32篇 |
2013年 | 49篇 |
2012年 | 61篇 |
2011年 | 68篇 |
2010年 | 38篇 |
2009年 | 50篇 |
2008年 | 35篇 |
2007年 | 56篇 |
2006年 | 42篇 |
2005年 | 41篇 |
2004年 | 38篇 |
2003年 | 53篇 |
2002年 | 52篇 |
2001年 | 30篇 |
2000年 | 26篇 |
1999年 | 33篇 |
1998年 | 10篇 |
1997年 | 5篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 7篇 |
1993年 | 7篇 |
1992年 | 10篇 |
1991年 | 11篇 |
1990年 | 12篇 |
1989年 | 10篇 |
1988年 | 11篇 |
1987年 | 6篇 |
1986年 | 5篇 |
1985年 | 11篇 |
1984年 | 11篇 |
1983年 | 6篇 |
1979年 | 5篇 |
1978年 | 9篇 |
1977年 | 8篇 |
1976年 | 3篇 |
1975年 | 7篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1971年 | 3篇 |
1969年 | 2篇 |
排序方式: 共有1057条查询结果,搜索用时 15 毫秒
1.
Generoso Gómez Cruz Miguel Barrueco Ferrero Irene Aparicio Coca José Ángel Maderuelo Miguel Torrecilla García 《Archivos de bronconeumologia》2009,45(1):16-23
Background and ObjectiveSchool smoking prevention programs have never yielded the expected results. The aim of this study was to analyze the efficacy of an intensive smoking prevention program created by the educational community in which it was to be applied.Population and MethodA 3-year smoking prevention program was carried out among the students of Fuentesaúco Secondary School in Zamora, Spain. The Babilafuente Secondary School in Salamanca, Spain was the control group. The program included both prevention and treatment activities. The former were carried out in the school, in out-of-school situations, and in the community. The questionnaire of the European Smoking Prevention Framework Approach was used.ResultsA total of 417 students aged 12 to 17 years participated in the study. Of these, 54.4% belonged to the intervention group and 45.6% to the control group. Smokers represented 36.7% of the population. After the intervention smokers represented 40.1% of the Fuentesaúco students compared with 46.1% of the Babilafuente students, though the difference was not statistically significant. With respect to the cognitive determinants of smoking behavior, after the intervention significant differences in favor of the intervention group were only observed in the subjects’ perception of the behavior of their siblings, peers, and teachers.ConclusionsThe use of smoking prevention programs in schools should be reconsidered, and their evaluation should be based on educational rather than clinical criteria. Proposed changes in the program include decreasing its intensity, starting with students of an earlier age and seeking greater involvement of parents. 相似文献
2.
3.
4.
Philippe Chauveau Benot Vendrely Wael El Haggan Nicole Barthe Vincent Rigalleau Christian Combe Michel Aparicio 《Journal of renal nutrition》2003,13(4):282-287
BACKGROUND: It has been reported that patients on a very-low-protein diet (VLPD) maintain a satisfactory nutritional status because of a conserved adaptive metabolic response. However, only few studies have examined the course of nutritional status and body composition in the long term (2 years). METHODS: Thirteen stable patients (8 men; age, 55 +/- 12 years; glomerular filtration rate (GFR), 15 +/- 5 mL/min) receiving a VLPD (0.3 g/kg/day protein) supplemented with amino acids and ketoanalogues (SVLPD) were studied for 2 years. A joint visit with a physician and a dietitian and routine blood and urine analyses were performed every month. Dual-energy x-ray absorptiometry (DEXA), which was used to assess modification of body composition, and GFR (urinary 51Cr-EDTA) and urinary urea and creatinine excretion, which were used to assess nutritional status and compliance to the diet, were assessed every 3 months. RESULTS: GFR, albumin, and prealbumin levels remained stable. Urea urinary excretion decreased at 3 months and then slightly increased at 2 years, but the calculated protein intake remained low at 0.38 +/- 0.1 g/kg/day. Energy intake remained close to 30 kcal/kg/day. No significant change was observed for total fat mass or percent fat mass. After an initial decrease, lean body mass stabilized at 6 months and then increased significantly from 6 to 24 months (P =.02, paired t-test); the mean increase during this period was of 2 kg, that is, 4.6%. Urinary creatinine excretion showed the same profile. Total bone mass, lumbar or hip site bone mass, and Z-score significantly decreased from T0 to 1 and 2 years (P <.05). CONCLUSION: This study confirms that a supplemented VLPD is nutritionally safe for a long period, but attention must be paid to bone mass. 相似文献
5.
J R Regueiro P Perez-Aeiego P Aparicio C Martinez P Morales A Arnaiz-Villena 《European journal of immunology》1990,20(11):2411-2416
B lymphocytes require appropriate T lymphocyte cooperation to synthesize immunoglobulins (Ig). Such interaction presumably takes place after engagement of the T cell receptor (TcR) by antigen. The present work addresses B lymphocyte function (and phenotype) in a novel type of immunodeficiency which is characterized by a TcR expression defect. In contrast to expectations, the two affected siblings that were studied displayed normal in vivo antibody responses to both endogenous and exogenous protein antigens. However, they showed impaired responses to certain polysaccharide antigens together with a selective IgG2 deficiency. These results suggest that some polysaccharide responses may be more T cell dependent than previously suspected, and support the notion that T cell dysfunctions (of this or other kind), rather than Ig gene deletions, may be the molecular basis of certain IgG2 deficiencies. To rule out a concomitant gross B cell dysfunction in these individuals, B lymphocyte phenotype and function were assayed in vitro, and found to be normal. A T cell line derived from one of the siblings displayed an abnormal TcR on the cell surface, but it showed several normal TcR-mediated functions. This suggests that the low number of peripheral T lymphocytes that have been found to express low TcR levels in these immunodeficiencies may be operational, and supplying sufficient "help" for the observed normal antibody responses to all tested protein, but not polysaccharide, antigens. 相似文献
6.
Clonal heterogeneity of HLA-B27 cellular allorecognition. Delineation of immunodominant sites 总被引:2,自引:0,他引:2
P Aparicio D Jaraquemada S Rojo J A López de Castro 《European journal of immunology》1988,18(2):203-209
The fine specificity of nine cytolytic T lymphocyte (CTL) clones obtained after stimulation of HLA-B27- responder lymphocytes with B27.1+ lymphoblastoid cell lines has been analyzed. These clones defined three different reaction patterns when tested against a panel of target cells including those expressing all known HLA-B27 subtypes: (a) specific recognition of HLA-B27.1, B27.2 and B27d, (b) selective reactivity with B27.1, B27d and HLA-B40 and (c) selective recognition of B27.1, B27.2, B27d, B27f and B40. Representative clones within each group were analyzed in detail. Differences in lytic ability of the various susceptible targets within each group were established by cold target inhibition analyses and by blocking experiments with anti-CD3 and anti-CD8 monoclonal antibodies. When correlated with the known structure of the HLA-B27 subtypes, these results demonstrate the critical relevance of amino acid changes within residues 77-81 and at position 152 in modulating allospecific CTL recognition of HLA-B27.1 and suggest that these residues could be involved in the structure of immunodominant regions of this antigen. The observed cross-reactions with HLA-B40, differing from B27.1 in 16 amino acid residues, suggest that the simultaneous occurrence of multiple amino acid changes could have mutually compensatory effects, so that a cross-reactive epitope might result from various combinations of polymorphic residues. 相似文献
7.
J M Aparicio A Wakisaka A Takada N Matsuura T Yoshiki 《The Japanese journal of human genetics》1989,34(4):269-277
Polymorphism in the genes encoding the alpha (alpha), beta (beta) and gamma (gamma) chains of the human T-cell receptors was analyzed both in population and family studies. Against twelve unrelated Japanese, several out of the 15 restriction endonucleases tested, revealed restriction fragment length polymorphism. The segregation of the polymorphic fragments were confirmed among 15 members of three families. In most of the cases paternal and/or maternal haplotypes could be assigned. By testing the polymorphic enzymes among the random healthy Japanese, the frequency of each polymorphic fragment was then determined. Although the polymorphism found in this study was similar to that reported in Caucasians, some differences were observed. Such differences are discussed. The restriction fragment length polymorphism in both population and family studies, derived from alpha, beta and gamma chains of the T-cell receptor found in this report, might be useful markers for genetic analysis of the T-cell function in relation to immunological disorders. 相似文献
8.
Sandford R; Sgotto B; Aparicio S; Brenner S; Vaudin M; Wilson RK; Chissoe S; Pepin K; Bateman A; Chothia C; Hughes J; Harris P 《Human molecular genetics》1997,6(9):1483-1489
PKD1 is the major locus of the common genetic disorder autosomal dominant
polycystic kidney disease (ADPKD). Analysis of the predicted protein
sequence of the human PKD1 gene, polycystin, shows a large molecule with a
unique arrangement of extracellular domains and multiple putative
transmembrane regions. The precise function of polycystin remains unclear
with a paucity of mutations to define key structural and functional
domains. To refine the structure of this protein we have cloned the genomic
region encoding the Fugu PKD1 gene. Fugu PKD1 spans 36 kb of genomic DNA
and has greater complexity with 54 exons compared with 46 in man.
Comparative analysis of the predicted protein sequences shows a lower level
of homology than in similar studies with identity of 40 and 59% similarity.
However key structural motifs including leucine rich repeats (LRR), a
C-type lectin and LDL-A like domains and 16 PKD repeats are maintained. A
region of homology with the sea urchin REJ protein was also confirmed in
Fugu but found to extend over 1000 amino acids. Several highly conserved
intra- and extra- cellular regions, with no known sequence homologies, that
are likely to be of functional importance were detected. The likely
structure of the membrane associated region has been refined with
similarity to the PKD2 protein and voltage gated Ca2+ and Na+ channels
highlighted over part of this area. The overall protein structure has
therefore been clarified and this comparative analysis derived structure
will form the basis for the functional study of polycystin and its
individual domains.
相似文献
9.
Trinidad Hernandez-Caselles Gonzalo Rubio Miguel R. Campanero Miguel Angel del Pozo M. Muro Francisco Sanchez-Madrid Pedro Aparicio 《European journal of immunology》1993,23(11):2799-2806
Optimal activation of human T cells mediated by ligation of CD3/T cell receptor (TcR) complex requires co-stimulatory signals. These can be provided by the adhesive interaction between receptor molecules on T cells and their counter-receptors on antigen-presenting cells. Soluble ICAM-3, anti-ICAM-3 and anti-CD3 mAb were utilized to address the role of the ICAM-3/LFA-1 pathway in TcR/CD3-dependent or -independent T cell activation. Immunoaffinity-purified ICAM-3 co-immobilized with suboptimal concentrations of anti-CD3 monoclonal antibody (mAb) stimulated T lymphocytes as monitored by the expression of the lymphocyte activation antigens CD25 and CD69. The mechanism underlaying this activation appear to involve the interaction of ICAM-3 with a β2 integrin, likely to be LFA-1, since mAb to the CD18 chain completely inhibited T cell activation. Similar experiments demonstrated that anti-ICAM-3 mAb were able to co-stimulate both resting (cord blood) and activated (T cell clones) T lymphocytes. On the contrary, anti-ICAM-1 mAb were only co-stimulatory for CD25 expression on activated but not on resting T cells. In addition, we have found that some γδ T cell clones bearing the Vδ1 segment were activated by direct mAb engagement of ICAM-3 in the absence of TcR/CD3 occupancy. Furthermore, immobilized anti-ICAM-3 mAb also induced development of dentritic processes. In conclusion, our data suggest that ICAM-3 on the surface of both T cells and antigen-presenting cells plays an essential role in the initiation of the immune response. 相似文献
10.
Flor-Alemany Marta Baena-García Laura Migueles Jairo H. Henriksson Pontus Löf Marie Aparicio Virginia A. 《Quality of life research》2022,31(9):2705-2716
Quality of Life Research - The relation between diet and maternal mental health during pregnancy might be relevant to prevent adverse materno-foetal outcomes. This study examined the association of... 相似文献