全文获取类型
收费全文 | 19058篇 |
免费 | 1492篇 |
国内免费 | 2篇 |
出版年
2023年 | 111篇 |
2022年 | 105篇 |
2021年 | 337篇 |
2020年 | 252篇 |
2019年 | 341篇 |
2018年 | 540篇 |
2017年 | 507篇 |
2016年 | 674篇 |
2015年 | 1020篇 |
2014年 | 1011篇 |
2013年 | 1315篇 |
2012年 | 1617篇 |
2011年 | 1443篇 |
2010年 | 961篇 |
2009年 | 828篇 |
2008年 | 1076篇 |
2007年 | 1068篇 |
2006年 | 954篇 |
2005年 | 881篇 |
2004年 | 857篇 |
2003年 | 762篇 |
2002年 | 773篇 |
2001年 | 343篇 |
2000年 | 352篇 |
1999年 | 291篇 |
1998年 | 186篇 |
1997年 | 110篇 |
1996年 | 121篇 |
1995年 | 101篇 |
1994年 | 92篇 |
1993年 | 84篇 |
1992年 | 149篇 |
1991年 | 119篇 |
1990年 | 124篇 |
1989年 | 96篇 |
1988年 | 93篇 |
1987年 | 79篇 |
1986年 | 97篇 |
1985年 | 80篇 |
1984年 | 82篇 |
1983年 | 67篇 |
1982年 | 68篇 |
1981年 | 48篇 |
1980年 | 38篇 |
1979年 | 39篇 |
1978年 | 24篇 |
1977年 | 21篇 |
1975年 | 30篇 |
1974年 | 23篇 |
1973年 | 33篇 |
排序方式: 共有10000条查询结果,搜索用时 171 毫秒
1.
Z. Kato Seiji Fukuda Shunji Tomatsu Hugo Vega Teruo Yasunaga Atsushi Yamagishi Naoto Yamada A. Valencia Luis Alejandro Barrera Kazuko Sukegawa Tadao Orii Naomi Kondo 《Human genetics》1997,101(1):97-101
Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive lysosomal storage disorder caused by a genetic defect in N-acetylgalactosamine-6-sulfate
sulfatase (GALNS). In previous studies, we have found two common mutations in Caucasians and Japanese, respectively. To characterize
the mutational spectrum in various ethnic groups, mutations in the GALNS gene in Colombian MPS IVA patients were investigated,
and genetic backgrounds were extensively analyzed to identify racial origin, based on mitochondrial DNA (mtDNA) lineages.
Three novel missense mutations never identified previously in other populations and found in 16 out of 19 Colombian MPS IVA
unrelated alleles account for 84.2% of the alleles in this study. The G301C and S162F mutations account for 68.4% and 10.5%
of mutations, respectively, whereas the remaining F69V is limited to a single allele. The skewed prevalence of G301C in only
Colombian patients and haplotype analysis by restriction fragment length polymorphisms in the GALNS gene suggest that G301C
originated from a common ancestor. Investigation of the genetic background by means of mtDNA lineages indicate that all our
patients are probably of native American descent.
Received: 2 January 1997 / Accepted: 10 June 1997 相似文献
2.
3.
High T cell epitope sharing between two HLA-B27 subtypes (B*2705 and B*2709) differentially associated to ankylosing spondylitis. 总被引:5,自引:0,他引:5
M García-Peydró M Martí J A López de Castro 《Journal of immunology (Baltimore, Md. : 1950)》1999,163(4):2299-2305
HLA-B*2705 is strongly associated with ankylosing spondylitis (AS) and reactive arthritis. In contrast, B*2709 has been reported to be more weakly or not associated to AS. These two molecules differ by a single amino acid change: aspartic acid in B*2705 or histidine in B*2709 at position 116. In this study, we analyzed the degree of T cell epitope sharing between the two subtypes. Ten allospecific T cell clones raised against B*2705, 10 clones raised against B*2703 but cross-reactive with B*2705, and 10 clones raised against B*2709 were examined for their capacity to lyse B*2705 and B*2709 target cells. The anti-B*2705 and anti-B*2703 CTL were peptide dependent as demonstrated by their failure to lyse TAP-deficient B*2705-T2 transfectant cells. Eight of the anti-B*2705 and five of the anti-B*2703 CTL clones lysed B*2709 targets. The degree of cross-reaction between B*2705 and B*2709 was donor dependent. In addition, the effect of the B*2709 mutation (D116H) on allorecognition was smaller than the effect of the other naturally occurring subtype change at this position, D116Y. These results demonstrate that B*2705 and B*2709 are the antigenically closest HLA-B27 subtypes. Because allospecific T cell recognition is peptide dependent, our results imply that the B*2705- and B*2709-bound peptide repertoires are largely overlapping. Thus, to the extent to which linkage of HLA-B27 with AS is related to the peptide-presenting properties of this molecule, our results would imply that peptides within a relatively small fraction of the HLA-B27-bound peptide repertoire influence susceptibility to this disease. 相似文献
4.
María José Arauz Valéry Ridde Libia Milena Hernández Yaneth Charris Mabel Carabali Luis ángel Villar 《PloS one》2015,10(2)
BackgroundDengue fever is a public health problem in the tropical and sub-tropical world. Dengue cases have grown dramatically in recent years as well as dengue mortality. Colombia has experienced periodic dengue outbreaks with numerous dengue related-deaths, where the Santander department has been particularly affected. Although social determinants of health (SDH) shape health outcomes, including mortality, it is not yet understood how these affect dengue mortality. The aim of this pilot study was to develop and pre-test a social autopsy (SA) tool for dengue mortality.ConclusionsThe SA tool is based on the scientific literature, a validated conceptual framework, researchers’ and health professionals’ expertise, and a pilot study. It is the first time that a SA tool has been created for the dengue mortality context. Our work furthers the study on SDH and how these are applied to neglected tropical diseases, like dengue. This tool could be integrated in surveillance systems to provide complementary information on the modifiable and avoidable death-related factors and therefore, be able to formulate interventions for dengue mortality reduction. 相似文献
5.
Paula A. Rudenick Bart H. Bijnens Patrick Segers David García-Dorado Arturo Evangelista 《PloS one》2015,10(4)
Descending aortic dissection (DAD) is associated with high morbidity and mortality rates. Aortic wall stiffness is a variable often altered in DAD patients and potentially involved in long-term outcome. However, its relevance is still mostly unknown. To gain more detailed knowledge of how wall elasticity (compliance) might influence intraluminal haemodynamics in DAD, a lumped-parameter model was developed based on experimental data from a pulsatile hydraulic circuit and validated for 8 clinical scenarios. Next, the variations of intraluminal pressures and flows were assessed as a function of wall elasticity. In comparison with the most rigid-wall case, an increase in elasticity to physiological values was associated with a decrease in systolic and increase in diastolic pressures of up to 33% and 63% respectively, with a subsequent decrease in the pressure wave amplitude of up to 86%. Moreover, it was related to an increase in multidirectional intraluminal flows and transition of behaviour as 2 parallel vessels towards a vessel with a side-chamber. The model supports the extremely important role of wall elasticity as determinant of intraluminal pressures and flow patterns for DAD, and thus, the relevance of considering it during clinical assessment and computational modelling of the disease. 相似文献
6.
Norma Diaz-Gustavo Martín Martínez-Salvador José Luís García-Hernández Mariano Norzagaray-Campos Antonio Luna-González Héctor Abelardo González-Ocampo 《PloS one》2015,10(5)
Caesalpinia platyloba was evaluated as an alternative for the retention of atmospheric carbon and as a feasible and viable economic activity in terms of income for tropical deciduous forest (TDF) peasants in the carbon markets. A total of 110 trees of C. platyloba from plantations and a TDF in the Northwest of Mexico were sampled. Growth (increase in height, diameter, and volume curves) was adjusted to assess their growth. Growth of individuals (height, diameter at breast height [DBH], age, and tree crown cover) was recorded. The Schumacher model (H = β0eβ1•E-1), by means of the guided curve method, was used to adjust growth models. Information analysis was made through the non-linear procedure with the multivariate secant or false position (DUD) method using the SAS software. Growth and increase models revealed acceptable adjustments (pseudo R2>0.8). C. platyloba reaches >8m of height with 12cm in diameter and 550cm3 of volume, presenting the highest increase at 11 years considered as basal age. Highest significant density of wood was in good quality sites (0.80g•cm-3), with a carbon content (average of 99.15tC•ha-1) at the highest density of 2500 trees•ha-1 (without thinning). Average incomes of US$483.33tC•ha-1 are expected. The profitability values (NPW = US$81,646.65, IRR = 472%, and B/C = 0.82) for C. platyloba make its cultivation a viable and profitable activity, considering a management scheme of the income derived from wood selling and from carbon credits. 相似文献
7.
Human Polμ is a DNA polymerase belonging to the X family that has been implicated in the non-homologous end-joining (NHEJ) pathway during repair of double-strand breaks in DNA. Loop1 is a flexible piece of Polμ which has a critical role during terminal transferase and end-joining activities: it acts as a pseudo-template when the template strand is discontinuous or unavailable, whilst diffusing away if present to avoid steric clashes. Mutational analysis and inspection of the 3D structures available allowed us to identify a network of residues in charge of sensing the presence or absence of discontinuities in the template strand, which will in turn determine the final position adopted by Loop1. This network is formed by the previously uncharacterized thumb mini-loop (NSH motif) and the positively charged helix N, which contribute to the correct positioning of Loop1 and to juxtapose the discontinuous template strand during NHEJ of incompatible ends. Accordingly, single mutation of specific conserved residues in these motifs, whilst irrelevant in most of the cases for gap filling, largely affected terminal transferase and end-joining activities. Other point mutations in the ‘hinges’ of Loop1, such as residues Phe385 or Phe389, corroborated the flexibility requirements of this motif. 相似文献
8.
Laura Garcia-Segura Cei Abreu-Goodger Armando Hernandez-Mendoza Tzvetanka D. Dimitrova Dinkova Luis Padilla-Noriega Martha Elva Perez-Andrade Juan Miranda-Rios 《PloS one》2015,10(11)
MicroRNAs (miRNAs) are non-coding RNAs of ~22 nucleotides in length that regulate gene expression by interfering with the stability and translation of mRNAs. Their expression is regulated during development, under a wide variety of stress conditions and in several pathological processes. In nature, animals often face feast or famine conditions. We observed that subjecting early L4 larvae from Caenorhabditis elegans to a 12-hr starvation period produced worms that are thinner and shorter than well-fed animals, with a decreased lipid accumulation, diminished progeny, reduced gonad size, and an increased lifespan. Our objective was to identify which of the 302 known miRNAs of C. elegans changed their expression under starvation conditions as compared to well-fed worms by means of deep sequencing in early L4 larvae. Our results indicate that 13 miRNAs (miR-34-3p, the family of miR-35-3p to miR-41-3p, miR-39-5p, miR-41-5p, miR-240-5p, miR-246-3p and miR-4813-5p) were upregulated, while 2 miRNAs (let-7-3p and miR-85-5p) were downregulated in 12-hr starved vs. well-fed early L4 larvae. Some of the predicted targets of the miRNAs that changed their expression in starvation conditions are involved in metabolic or developmental process. In particular, miRNAs of the miR-35 family were upregulated 6–20 fold upon starvation. Additionally, we showed that the expression of gld-1, important in oogenesis, a validated target of miR-35-3p, was downregulated when the expression of miR-35-3p was upregulated. The expression of another reported target, the cell cycle regulator lin-23, was unchanged during starvation. This study represents a starting point for a more comprehensive understanding of the role of miRNAs during starvation in C. elegans. 相似文献
9.
Luis Santamaría Jesús Balsa Beatriz Bidondo Angel Baltanás Carlos Montes 《Hydrobiologia》1992,246(2):89-98
Laboratory experiments and field data were used to determine salinity tolerance limits of three ostracode species (Prionocypris aragonica, Eucypris mareotica and Heterocypris barbara) from Iberian saline lakes. Salinity tolerance appeared related to ionic composition and temperature. Implications for ostracode ecology and geographical distribution are evaluated. 相似文献
10.