全文获取类型
收费全文 | 4675篇 |
免费 | 299篇 |
国内免费 | 26篇 |
专业分类
耳鼻咽喉 | 77篇 |
儿科学 | 150篇 |
妇产科学 | 100篇 |
基础医学 | 832篇 |
口腔科学 | 146篇 |
临床医学 | 450篇 |
内科学 | 818篇 |
皮肤病学 | 93篇 |
神经病学 | 655篇 |
特种医学 | 122篇 |
外科学 | 388篇 |
综合类 | 26篇 |
一般理论 | 2篇 |
预防医学 | 314篇 |
眼科学 | 180篇 |
药学 | 284篇 |
中国医学 | 23篇 |
肿瘤学 | 340篇 |
出版年
2024年 | 4篇 |
2023年 | 41篇 |
2022年 | 53篇 |
2021年 | 80篇 |
2020年 | 76篇 |
2019年 | 104篇 |
2018年 | 95篇 |
2017年 | 120篇 |
2016年 | 118篇 |
2015年 | 134篇 |
2014年 | 140篇 |
2013年 | 228篇 |
2012年 | 386篇 |
2011年 | 354篇 |
2010年 | 213篇 |
2009年 | 207篇 |
2008年 | 322篇 |
2007年 | 359篇 |
2006年 | 323篇 |
2005年 | 296篇 |
2004年 | 308篇 |
2003年 | 271篇 |
2002年 | 259篇 |
2001年 | 44篇 |
2000年 | 27篇 |
1999年 | 61篇 |
1998年 | 64篇 |
1997年 | 61篇 |
1996年 | 42篇 |
1995年 | 22篇 |
1994年 | 21篇 |
1993年 | 17篇 |
1992年 | 12篇 |
1991年 | 18篇 |
1990年 | 9篇 |
1989年 | 12篇 |
1988年 | 7篇 |
1987年 | 10篇 |
1986年 | 6篇 |
1985年 | 8篇 |
1984年 | 7篇 |
1983年 | 7篇 |
1982年 | 5篇 |
1981年 | 7篇 |
1980年 | 6篇 |
1978年 | 9篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1974年 | 3篇 |
1961年 | 2篇 |
排序方式: 共有5000条查询结果,搜索用时 0 毫秒
51.
Brock A. Peters Bahram G. Kermani Oleg Alferov Misha R. Agarwal Mark A. McElwain Natali Gulbahce Daniel M. Hayden Y. Tom Tang Rebecca Yu Zhang Rick Tearle Birgit Crain Renata Prates Alan Berkeley Santiago Munné Radoje Drmanac 《Genome research》2015,25(3):426-434
Currently, the methods available for preimplantation genetic diagnosis (PGD) of in vitro fertilized (IVF) embryos do not detect de novo single-nucleotide and short indel mutations, which have been shown to cause a large fraction of genetic diseases. Detection of all these types of mutations requires whole-genome sequencing (WGS). In this study, advanced massively parallel WGS was performed on three 5- to 10-cell biopsies from two blastocyst-stage embryos. Both parents and paternal grandparents were also analyzed to allow for accurate measurements of false-positive and false-negative error rates. Overall, >95% of each genome was called. In the embryos, experimentally derived haplotypes and barcoded read data were used to detect and phase up to 82% of de novo single base mutations with a false-positive rate of about one error per Gb, resulting in fewer than 10 such errors per embryo. This represents a ∼100-fold lower error rate than previously published from 10 cells, and it is the first demonstration that advanced WGS can be used to accurately identify these de novo mutations in spite of the thousands of false-positive errors introduced by the extensive DNA amplification required for deep sequencing. Using haplotype information, we also demonstrate how small de novo deletions could be detected. These results suggest that phased WGS using barcoded DNA could be used in the future as part of the PGD process to maximize comprehensiveness in detecting disease-causing mutations and to reduce the incidence of genetic diseases.Worldwide, more than 5 million babies (Ferraretti et al. 2013) have been born through in vitro fertilization (IVF) since the birth of the first in 1978 (Steptoe and Edwards 1978). Exact numbers are difficult to determine, but it has been estimated that currently 350,000 babies are born yearly through IVF (de Mouzon et al. 2009, 2012; Centers for Disease Control and Prevention 2011; Ferraretti et al. 2013). That number is expected to rise, as advanced maternal age is associated with decreased fertility rates and women in developed countries continue to delay childbirth to later ages. In 95% of IVF procedures, no diagnostic testing of the embryos is performed (https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?ClinicPKID=0). Couples with prior difficulties conceiving or those wishing to avoid the transmission of highly penetrant heritable diseases often choose to perform preimplantation genetic diagnosis (PGD). PGD involves the biopsy of one cell from a 3-d embryo or the recently more preferred method, due to improved implantation success rates (Scott et al. 2013b), of up to 10 cells from a 5- to 6-d blastocyst-stage embryo. Following biopsy, genetic analysis is performed on the isolated cell(s). Currently this is an assay for translocations and the correct chromosome copy number (Hodes-Wertz et al. 2012; Munne 2012; Yang et al. 2012; Scott et al. 2013a; Yin et al. 2013), a unique test designed and validated for each specific heritable disease (Gutierrez-Mateo et al. 2009), or a combination of both (Treff et al. 2013). Importantly, none of these approaches can detect de novo mutations.Advanced maternal age has long been associated with an increased risk of producing aneuploid embryos (Munne et al. 1995; Crow 2000; Hassold and Hunt 2009) and giving birth to a child afflicted with Down syndrome or other diseases resulting from chromosomal copy number alterations. Conversely, children of older fathers have been shown to have an increase in single base and short multibase insertion/deletion (indels) de novo mutations (Kong et al. 2012). Many recent large-scale sequencing studies have found that de novo variations spread across many different genes are likely to be the cause of a large fraction of autism cases (Michaelson et al. 2012; O’Roak et al. 2012; Sanders et al. 2012; De Rubeis et al. 2014; Iossifov et al. 2014), severe intellectual disability (Gilissen et al. 2014), epileptic encephalopathies (Epi4K Consortium and Epilepsy Phenome/Genome Project 2013), and many other congenital disorders (de Ligt et al. 2012; Veltman and Brunner 2012; Yang et al. 2013; Al Turki et al. 2014). Additionally rare and de novo variations have been suggested to be prevalent in patients with schizophrenia (Fromer et al. 2014; Purcell et al. 2014), and Michaelson et al. (2012) found that single base de novo mutations affect conserved regions of the genome and essential genes more often than regions of unknown function. Current targeted approaches to PGD would miss many of these important functional changes within the embryonic DNA sequence, and even a whole-genome sequencing (WGS)–based carrier screen of both parents would not enable comprehensive preimplantation or prenatal diagnoses due to de novo mutations. As more parents delay childbirth into their mid-30s and later, these studies suggest we should try to provide better diagnostic tests for improving the health of newborns. In this study, we demonstrate the use of an advanced WGS process that provides an accurate and phased genome sequence from about 10 cells, allowing highly sensitive and specific detection of single base de novo mutations from IVF blastocyst biopsies. 相似文献
52.
53.
54.
55.
This is to review the current state of knowledge on the functional and clinical aspects of bestrophin 1, a prominent member of a family of proteins involved in the control and properties of the light peak of the EOG. Initially human bestrophin 1 gene (BEST1) mutations were identified to underlie Best vitelliform macular dystrophy (VMD), a dominantly inherited, juvenile-onset form of macular degeneration. In the recent past the phenotypical spectrum of retinal disorders associated with BEST1 mutations has been extended and the term bestrophinopathies was coined. The physiological role of bestrophin 1 is still not completely understood but has been linked to the generation of a transepithelial chloride current by controlling voltage-dependent calcium channels (VDCC). Dysfunction of bestrophin 1 may result in abnormal ion and fluid transport by the retinal pigment epithelium (RPE) disturbing and even disrupting direct interactions between the RPE and the photoreceptors. 相似文献
56.
57.
Olga Moser Martin Zimmermann Ulrike Meyer Wolfram Klapper Ilske Oschlies Martin Schrappe Andishe Attarbaschi Georg Mann Felix Niggli Claudia Spix Udo Kontny Thomas Klingebiel Alfred Reiter Birgit Burkhardt Wilhelm Woessmann 《Haematologica》2021,106(5):1390
Second malignant neoplasms (SMN) pose a concern for survivors of childhood cancer. We evaluated incidence, type and risk factors for SMN in patients included in Berlin-Frankfurt-Muenster protocols for childhood non-Hodgkin lymphoma.3,590 patients <15 years of age at diagnosis, registered between 01/1981 and 06/2010, were analyzed. SMN were reported by the treating institutions and the German Childhood Cancer Registry. After a median follow-up of 9.4 years (quartile [Q] range, Q1 6.7 and Q3 12.1) 95 SMN were registered (26 carcinomas including nine basal cell carcinomas, 21 acute myeloid leukemias/myelodysplastic syndromes, 20 lymphoid malignancies, 12 central nervous system [CNS]-tumors, and 16 others). Cumulative incidence at 20 years was 5.7±0.7%, standard incidence ratio, excluding basal cell carcinomas, was 19.8 (95% Confidence Interval [CI]: 14.5-26.5). Median time from initial diagnosis to second malignancy was 8.7 years (range, 0.2-30.3 years). Acute-lymphoblasticleukemia- type therapy, cumulative anthracycline dose, and cranial radiotherapy for brain tumor-development were significant risk factors in univariate analysis only. In multivariate analysis including risk factors significant in univariate analysis, female sex (hazard ratio [HR] 1.87, 95% CI: 1.23-2.86, P=0.004), CNS-involvement (HR 2.24, 95% CI: 1.03-4.88, P=0.042), lymphoblastic lymphoma (HR 2.60, 95% CI: 1.69-3.97, P<0.001), and cancer-predisposing condition (HR 11.2, 95% CI: 5.52-22.75, P<0.001) retained an independent risk. Carcinomas were the most frequent SMN after non-Hodgkin lymphoma in childhood followed by acute myeloid leukemia and lymphoid malignancies. Female sex, lymphoblastic lymphoma, CNS-involvement, or/and known cancer-predisposing condition were risk factors for SMN-development. Our findings set the basis for individualized long-term follow-up and risk assessment of new therapies. 相似文献
58.
59.
Birgit Pfaller Samuel C. Siu Rohan D'Souza Barbara Wichert-Schmitt Govind Krishna Kumar Nair Kim Haberer Cynthia Maxwell Candice K. Silversides 《Journal of the American College of Cardiology》2021,77(10):1317-1326
BackgroundWomen with heart disease are at risk for complications during pregnancy. This study sought to examine the effect of maternal obesity on pregnancy complications in women with heart disease.ObjectivesThe objective was to determine the incidence of adverse cardiac events (CE) in pregnant women with heart disease and obesity.MethodsAdverse CE during pregnancy were examined in a prospective cohort of women with heart disease. CE were a composite of the following: cardiac death/arrest, arrhythmias, heart failure, myocardial infarction, stroke, aortic dissection, and thromboembolic events. Pre-eclampsia and post-partum hemorrhage were also studied. Outcomes were examined according to body mass index (BMI). To identify additional predictors of CE, a baseline risk score (CARPREG [Canadian Cardiac Disease in Pregnancy Study] II score) for predicting cardiac complications was calculated for all pregnancies and included in a multivariable logistic regression model.ResultsOf 790 pregnancies, 19% occurred in women with BMI ≥30 kg/m2 (obesity), 25% in women with BMI 25 to 29.9 kg/m2 (overweight), 53% in women with BMI 18.5 to 24.9 kg/m2 (normal weight), and 3% in women with BMI <18.5 kg/m2 (underweight). Women with obesity were at higher risk of CE when compared with women with normal weight (23% vs. 14%; p = 0.006). In a multivariable model, obesity (odds ratio: 1.7; 95% confidence interval: 1.0 to 2.7) and higher CARPREG II risk scores (odds ratio: 1.7; 95% confidence interval: 1.5 to 1.9) predicted CE. Pre-eclampsia was more frequent in women with obesity compared with those with normal weight (8% vs. 2%; p = 0.001).ConclusionsObesity increases the risk of maternal cardiovascular complications in pregnant women with heart disease. This modifiable risk factor should be addressed at the time of preconception counseling. 相似文献
60.
Birgit E J Teunissen Habo J Jongsma Marti F A Bierhuizen 《European heart journal》2004,25(22):1979-1989
Cardiac hypertrophic remodelling, initiated by signalling cascades in response to increased workload, injury or intrinsic disease, is initially adaptive. However, prolonged hypertrophy as a consequence of pathological stress leads to maladaptive changes that increase the risk for fatal ventricular arrhythmias. One of these changes is the remodelling of myocardial gap junctions, which provide for electrical coupling of adjacent cardiomyocytes. Myocardial gap junctions are composed of three connexin isotypes, connexin40 (Cx40), -43 (Cx43), and -45 (Cx45) and each display a characteristic developmental and regional expression pattern. Alterations in the distribution and expression of Cx43, the predominant isoform in the adult ventricles, has been the main focus of examination in humans, experimental animal models and cultured cardiomyocytes in response to hypertrophy. The molecular mechanisms and signalling pathways underlying these changes have been studied less thoroughly. In this review we summarize what is known about the remodelling of myocardial gap junctions during hypertrophy, the putative underlying mechanisms and functional consequences thereof. 相似文献