全文获取类型
收费全文 | 47757篇 |
免费 | 3466篇 |
国内免费 | 10篇 |
出版年
2023年 | 275篇 |
2022年 | 313篇 |
2021年 | 689篇 |
2020年 | 636篇 |
2019年 | 637篇 |
2018年 | 1114篇 |
2017年 | 1021篇 |
2016年 | 1617篇 |
2015年 | 2443篇 |
2014年 | 2463篇 |
2013年 | 3192篇 |
2012年 | 4229篇 |
2011年 | 3883篇 |
2010年 | 2231篇 |
2009年 | 1861篇 |
2008年 | 3109篇 |
2007年 | 2982篇 |
2006年 | 2863篇 |
2005年 | 2567篇 |
2004年 | 2498篇 |
2003年 | 2298篇 |
2002年 | 2148篇 |
2001年 | 792篇 |
2000年 | 856篇 |
1999年 | 544篇 |
1998年 | 367篇 |
1997年 | 243篇 |
1996年 | 259篇 |
1995年 | 263篇 |
1994年 | 226篇 |
1993年 | 190篇 |
1992年 | 199篇 |
1991年 | 176篇 |
1990年 | 166篇 |
1989年 | 135篇 |
1988年 | 113篇 |
1987年 | 86篇 |
1986年 | 82篇 |
1985年 | 122篇 |
1984年 | 162篇 |
1983年 | 83篇 |
1982年 | 104篇 |
1981年 | 78篇 |
1980年 | 86篇 |
1979年 | 70篇 |
1978年 | 65篇 |
1977年 | 64篇 |
1976年 | 80篇 |
1975年 | 66篇 |
1974年 | 55篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
911.
Andrés Moreno-Estrada Simon Gravel Fouad Zakharia Jacob L. McCauley Jake K. Byrnes Christopher R. Gignoux Patricia A. Ortiz-Tello Ricardo J. Martínez Dale J. Hedges Richard W. Morris Celeste Eng Karla Sandoval Suehelay Acevedo-Acevedo Paul J. Norman Zulay Layrisse Peter Parham Juan Carlos Martínez-Cruzado Esteban González Burchard Michael L. Cuccaro Eden R. Martin Carlos D. Bustamante 《PLoS genetics》2013,9(11)
The Caribbean basin is home to some of the most complex interactions in recent history among previously diverged human populations. Here, we investigate the population genetic history of this region by characterizing patterns of genome-wide variation among 330 individuals from three of the Greater Antilles (Cuba, Puerto Rico, Hispaniola), two mainland (Honduras, Colombia), and three Native South American (Yukpa, Bari, and Warao) populations. We combine these data with a unique database of genomic variation in over 3,000 individuals from diverse European, African, and Native American populations. We use local ancestry inference and tract length distributions to test different demographic scenarios for the pre- and post-colonial history of the region. We develop a novel ancestry-specific PCA (ASPCA) method to reconstruct the sub-continental origin of Native American, European, and African haplotypes from admixed genomes. We find that the most likely source of the indigenous ancestry in Caribbean islanders is a Native South American component shared among inland Amazonian tribes, Central America, and the Yucatan peninsula, suggesting extensive gene flow across the Caribbean in pre-Columbian times. We find evidence of two pulses of African migration. The first pulse—which today is reflected by shorter, older ancestry tracts—consists of a genetic component more similar to coastal West African regions involved in early stages of the trans-Atlantic slave trade. The second pulse—reflected by longer, younger tracts—is more similar to present-day West-Central African populations, supporting historical records of later transatlantic deportation. Surprisingly, we also identify a Latino-specific European component that has significantly diverged from its parental Iberian source populations, presumably as a result of small European founder population size. We demonstrate that the ancestral components in admixed genomes can be traced back to distinct sub-continental source populations with far greater resolution than previously thought, even when limited pre-Columbian Caribbean haplotypes have survived. 相似文献
912.
913.
María J. López-Armada Romina R. Riveiro-Naveira Carlos Vaamonde-García Marta N. Valcárcel-Ares 《Mitochondrion》2013,13(2):106-118
Inflammation has been linked to multiple degenerative and acute diseases as well as the aging process. Moreover, mitochondrial alterations play a central role in these processes. Mitochondria have an important role in pro-inflammatory signaling; similarly, pro-inflammatory mediators may also alter mitochondrial function. Both of these processes increase mitochondrial oxidative stress, promoting a vicious inflammatory cycle. Additionally, damage-associated molecular patterns derived from mitochondria could contribute to inflammasome formation and caspase-1 activation, while alterations in mitochondrial autophagy may cause inflammation. Strategies aimed at controlling excessive oxidative stress within mitochondria may represent both preventive and therapeutic interventions in inflammation. 相似文献
914.
Sofia Benfeito Catarina Oliveira Pedro Soares Carlos Fernandes Tiago Silva José Teixeira Fernanda Borges 《Mitochondrion》2013,13(5):427-435
The therapeutic potential of natural phenolic antioxidants in human diseases associated with oxidative damage has received great attention to date. Appraisal of literature evidences that, in general, antioxidant therapy has enjoyed relative successes in preclinical studies but little benefits in human intervention studies or clinical trials. In fact, despite the huge, largely untapped potential therapeutic benefit of natural phenolic antioxidants, such as vitamins, non-flavonoid and flavonoid compounds, they appear not to be suitable drug candidates. The problem may be related, among others, to their non-drug-likeness properties. Though controversial the results obtained so far confirm the importance of exploring phenolic natural systems as safe templates for the design of new antioxidants. To support the assumption an outlook of the lead structural optimization process to improve ADME properties was given by means of natural hydroxycinnamic acids as a case study. The optimization of drug physicochemical properties and the development of appropriate delivery antioxidant systems can provide in the next future a way out to attain effective therapeutic antioxidant agents. 相似文献
915.
Carla Rossini Crepaldi Phelipe Augusto Mariano Vitale Andrea Cristina Tesch Hélen Julie Laure José César Rosa Marcelo de Cerqueira César 《Mitochondrion》2013,13(6):823-830
Two types of binding sites for hexokinase, designated as Type A or Type B sites, have been shown to coexist on brain mitochondria. The ratio of these sites varies between species.HK1 attaches by reversibly binding to the voltage dependent anion channel (VDAC). Regarding the nature of hexokinase binding sites, we investigated if it was linked to distinct VDAC interactomes. We approached this question by 2D BN/SDS-PAGE of mitochondria, followed by mass spectrometry.Our results are consistent with the possibility that the ratio of Type A/Type B sites is due to differential VDAC interactions in bovine and rat neuronal cells. 相似文献
916.
917.
Oscar Ortega-Recalde Dora Janeth Fonseca Liliana Catherine Patiño Juan Jaime Atuesta Carolina Rivera-Nieto Carlos Martín Restrepo Heidi Eliana Mateus Marjo S. van der Knaap Paul Laissue 《Mitochondrion》2013,13(6):749-754
NDUFV1 mutations have been related to encephalopathic phenotypes due to mitochondrial energy metabolism disturbances. In this study, we report two siblings affected by a diffuse leukodystrophy, who carry the NDUFV1 c.1156C>T (p.Arg386Cys) missense mutation and a novel 42-bp deletion. Bioinformatic and molecular analysis indicated that this deletion lead to the synthesis of mRNA molecules carrying a premature stop codon, which might be degraded by the nonsense-mediated decay system. Our results add information on the molecular basis and the phenotypic features of mitochondrial disease caused by NDUFV1 mutations. 相似文献
918.
Germana Bueno Dias Valdirene Moreira Gomes Umberto Zottich Pereira Suzanna F. Ferreira Ribeiro André O. Carvalho Rosana Rodrigues Olga L. Tavares Machado Kátia Valevski Sales Fernandes André Teixeira S. Ferreira Jonas Perales Maura Da Cunha 《The protein journal》2013,32(1):15-26
Capsicum species belong to the Solanaceae family and have great social, economic and agronomical significance. The present research presents data on the isolation and characterization of Capsicum chinense Jacq. peptides which were scrutinized in relation to their toxicity towards a diverse set of yeast species. The protein extract was separated with C18 reverse-phase chromatography in high performance liquid chromatography, resulting in three different peptide enriched fractions (PEFs) termed PEF1, PEF2 and PEF3. Tricine-SDS-PAGE of the PEF2 revealed peptides with molecular masses of approximately 5.0 and 8.5 kDa. These PEFs also exhibited strong antifungal activity against different yeasts. In the presence of the PEF2, Candida tropicalis exhibited morphological changes, including cellular agglomeration and formation of pseudohyphae. Determined N-terminal sequences of PEF2 and PEF3 were proven to be highly homologous to serine proteinase inhibitors, when analysed by comparative database sequence tools. For this reason were performed protease inhibitory activity assay. The PEFs displayed high inhibitory activity against trypsin and low inhibitory activity against chymotrypsin. PEF2 and PEF3 were considerably unsusceptible to a broad interval of pH and temperatures. Due to the myriad of application of Proteinase inhibitors (PIs) in fields ranging from plant protection against pathogens and pests to medicine such as in cancer and virus replication inhibition, the discovery of new PIs with new properties are of great interest. 相似文献
919.
Emilio García García María-Ángeles Vázquez López Rafael Galera Martínez Irene Alias Manuel Martín González Antonio Bonillo Perales José Eugenio Cabrera Sevilla Icíar García Escobar Sara Gómez Bueno Encarnación López Ruzafa Francisco-Javier Muñoz Vico Patricia Oliva Pérez María Ortiz Pérez Juan Poveda González Marisa Rodríguez Lucenilla Firma-Isabel Rodríguez Sánchez Ana Ruiz Sánchez Lucía Ruiz Tudela Sara Torrico 《Endocrinología y nutrición》2013,60(3):121-126
ObjectivesTo estimate the prevalence of obesity and overweight in children and adolescents in our city and to investigate the associated factors.Subjects and methodsA cross-sectional study of 1317 children and adolescents aged 2-16 years. Multistage probability sampling was used to select three groups of subjects: 411 aged 12 to 16 years, 504 aged 6 to 12 years, and 402 aged 2 to 6 years. Body mass index was calculated, and obesity and overweight were diagnosed using the threshold levels of the International Obesity Task Force for children and adolescents. Parents were asked about eating habits, health, social, and demographic aspects. Results are given as percentages (95% confidence interval). The relationship between obesity and overweight and the different variables was studied using multiple logistic regression. The adjusted odds ratio (OR) was calculated.ResultsAmong children and adolescentes aged 2-16 years, 9.5% (8.0%-11.0%) were obese and 22.4% (23.3%-24.6%) were overweight. Of subjects aged 12-16 years, 8.5% (5.9%-11.2%) were obese and 20.5% (16.7%-24.3%) were overweight. In the groups aged 6-12 years and 2-6 years, rates of obesity and overweight were 11.6% (8.9% -14.3%) and 31.0% (27.0-35.0) and 8.0% (5.4%-10.6%) and 13.6% (10.3%-16.9%) respectively. Obesity or overweight was associated to age (OR 1.21; P< 0.001), maternal obesity (OR 10.99; P= 0.008), a birthweight higher than 4 kg (OR 2.91; p 0.002), and formula feeding (OR 1.82; P= 0.005).ConclusionObesity and overweight in children and adolescents are highly prevalent problems in our city. 相似文献
920.
Kazuhiro Tajima-Pozo Ana Montes-Montero Itziar Güemes Sara González-Vives Marina Díaz-Marsá José Luis Carrasco 《Endocrinología y nutrición》2013,60(7):396-403
Activity of the hypothalamic-pituitary-adrenal axis had been studied for the past half century, when some researchers noted that some patients with Cushing's syndrome and severe mood disorders had high baseline cortisol levels, which resulted in an inhibited response in the 1 mg dexamethasone suppression test. Altered dexamethasone suppression test results were subsequently found in many psychiatric diseases, including anorexia nervosa, obsessive-compulsive disorder, degenerative dementia, bipolar disorders, and schizophrenia. The relationship between high baseline cortisol levels and stress has also been studied. Some researches on the genesis of borderline personality disorder focused on traumatic childhood backgrounds. Other investigations aimed at elucidating the relationship between traumatic backgrounds and some psychiatric disorders noted that patients with post-traumatic stress disorder and borderline personality disorder showed an enhanced cortisol suppression with low cortisol doses (0.5 mg). Recent studies showed that use of an ultra-low dose of cortisol during the dexamethasone suppression test may be helpful for deteting disorders with hyperactivity of the hypothalamic-pituitary-adrenal axis.Recent advances in neuroimaging support the existence of hyperactivity of the hypothalamic-pituitary-adrenal axis in patients with borderline personality disorder, relating a decreased pituitary gland volume to major traumatic backgrounds and suicidal attempts. The purpose of this paper is to make a narrative review of research using dexamethasone suppression test in psychiatric disorders, in order to ascertain its value as a supplemental diagnostic test or as a prognostic marker. 相似文献