全文获取类型
收费全文 | 43446篇 |
免费 | 3332篇 |
国内免费 | 7篇 |
出版年
2023年 | 243篇 |
2022年 | 204篇 |
2021年 | 550篇 |
2020年 | 521篇 |
2019年 | 558篇 |
2018年 | 1012篇 |
2017年 | 922篇 |
2016年 | 1466篇 |
2015年 | 2251篇 |
2014年 | 2213篇 |
2013年 | 2923篇 |
2012年 | 3883篇 |
2011年 | 3586篇 |
2010年 | 2050篇 |
2009年 | 1697篇 |
2008年 | 2823篇 |
2007年 | 2685篇 |
2006年 | 2641篇 |
2005年 | 2343篇 |
2004年 | 2309篇 |
2003年 | 2096篇 |
2002年 | 1989篇 |
2001年 | 767篇 |
2000年 | 839篇 |
1999年 | 516篇 |
1998年 | 349篇 |
1997年 | 195篇 |
1996年 | 219篇 |
1995年 | 228篇 |
1994年 | 207篇 |
1993年 | 190篇 |
1992年 | 195篇 |
1991年 | 151篇 |
1990年 | 153篇 |
1989年 | 132篇 |
1988年 | 106篇 |
1987年 | 83篇 |
1986年 | 82篇 |
1985年 | 114篇 |
1984年 | 147篇 |
1983年 | 87篇 |
1982年 | 108篇 |
1981年 | 83篇 |
1980年 | 79篇 |
1979年 | 73篇 |
1978年 | 54篇 |
1977年 | 55篇 |
1976年 | 74篇 |
1975年 | 65篇 |
1974年 | 52篇 |
排序方式: 共有10000条查询结果,搜索用时 109 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.
E San José A Benguría P Geller A Villalobo 《The Journal of biological chemistry》1992,267(21):15237-15245
We demonstrate in this report that the epidermal growth factor (EGF) receptor from rat liver can be isolated by calmodulin affinity chromatography by binding in the presence of Ca2+ and elution with a Ca(2+)-chelating agent. The bulk of the EGF receptor is not eluted by a NaCl gradient in the presence of Ca2+. We ascertained the identity of the isolated receptor by immunoblot and immunoprecipitation using a polyclonal antibody against an EGF receptor from human origin. The purified receptor is autophosphorylated in tyrosine residues in an EGF-stimulated manner, and EGF-dependent phosphorylation of serine residues was also detected. Both the EGF and the transforming growth factor-alpha stimulate the tyrosine-directed protein kinase activity of the isolated receptor with similar affinities. Furthermore, we demonstrate that calmodulin inhibits the EGF-dependent tyrosine-directed protein kinase activity associated to the receptor in a concentration-dependent manner. This inhibition is partially Ca2+ dependent and is not displaced by increasing the concentration of EGF up to an EGF/calmodulin ratio of 10 (mol/mol). In addition, calmodulin was phosphorylated in an EGF-stimulated manner in the presence of a basic protein (histone) as cofactor and in the absence, but not in the presence, of Ca2+. 相似文献
4.
Ouajdi Korbaa Hervé Camus Jean-Claude Gentina 《Flexible Services and Manufacturing Journal》2002,14(2):173-187
Flexible manufacturing system control is an NP-hard problem. A cyclic approach has been demonstrated to be adequate for an infinite scheduling problem because of maximal throughput reachability. However, it is not the only optimization criterion in general. In this article we consider the minimization of the work in process (WIP) as an economical and productivity factor. We propose a new cyclic scheduling algorithm giving the maximal throughput (a hard constraint) while minimizing WIP. This algorithm is based on progressive operations placing. A controlled beam search approach has been developed to determine at each step the schedule of the next operations. After presenting the main principles of the algorithm, we compare our approach to several most known cyclic scheduling algorithms using a significant existing example from the literature. 相似文献
5.
ágnes Lendvai Frank Johannes Christina Grimm Jasper J.H. Eijsink René Wardenaar Haukeline H. Volders Harry G. Klip Harry Hollema Ritsert C. Jansen Ed Schuuring G. Bea A. Wisman Ate G.J. van der Zee 《Epigenetics》2012,7(11):1268-1278
Epigenetic modifications, such as aberrant DNA promoter methylation, are frequently observed in cervical cancer. Identification of hypermethylated regions allowing discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3), or worse, may improve current cervical cancer population-based screening programs. In this study, the DNA methylome of high-grade CIN lesions was studied using genome-wide DNA methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methylated DNA Immunoprecipitation (MeDIP) combined with DNA microarray was used to compare DNA methylation profiles of epithelial cells derived from high-grade CIN lesions with normal cervical epithelium. Hypermethylated differentially methylated regions (DMRs) were identified. Validation of nine selected DMRs using BSP and MSP in cervical tissue revealed methylation in 63.2–94.7% high-grade CIN and in 59.3–100% cervical carcinomas. QMSP for the two most significant high-grade CIN-specific methylation markers was conducted exploring test performance in a large series of cervical scrapings. Frequency and relative level of methylation were significantly different between normal and cancer samples. Clinical validation of both markers in cervical scrapings from patients with an abnormal cervical smear confirmed that frequency and relative level of methylation were related with increasing severity of the underlying CIN lesion and that ROC analysis was discriminative. These markers represent the COL25A1 and KATNAL2 and their observed increased methylation upon progression could intimate the regulatory role in carcinogenesis. In conclusion, our newly identified hypermethylated DMRs represent specific DNA methylation patterns in high-grade CIN lesions and are candidate biomarkers for early detection. 相似文献
6.
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
7.
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
8.
9.
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
10.
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