全文获取类型
收费全文 | 19601篇 |
免费 | 1873篇 |
国内免费 | 1098篇 |
出版年
2024年 | 57篇 |
2023年 | 527篇 |
2022年 | 738篇 |
2021年 | 1063篇 |
2020年 | 862篇 |
2019年 | 1048篇 |
2018年 | 959篇 |
2017年 | 729篇 |
2016年 | 808篇 |
2015年 | 969篇 |
2014年 | 1291篇 |
2013年 | 1659篇 |
2012年 | 928篇 |
2011年 | 1078篇 |
2010年 | 779篇 |
2009年 | 941篇 |
2008年 | 921篇 |
2007年 | 852篇 |
2006年 | 821篇 |
2005年 | 765篇 |
2004年 | 692篇 |
2003年 | 515篇 |
2002年 | 487篇 |
2001年 | 393篇 |
2000年 | 301篇 |
1999年 | 270篇 |
1998年 | 267篇 |
1997年 | 245篇 |
1996年 | 192篇 |
1995年 | 165篇 |
1994年 | 212篇 |
1993年 | 148篇 |
1992年 | 145篇 |
1991年 | 96篇 |
1990年 | 102篇 |
1989年 | 63篇 |
1988年 | 72篇 |
1987年 | 50篇 |
1986年 | 45篇 |
1985年 | 50篇 |
1984年 | 38篇 |
1983年 | 42篇 |
1982年 | 41篇 |
1981年 | 35篇 |
1980年 | 18篇 |
1979年 | 25篇 |
1978年 | 17篇 |
1976年 | 12篇 |
1975年 | 10篇 |
1974年 | 11篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
971.
Genes involved in cellular mechanisms to repair oxidative damage are strong candidates as etiologic factors for Alzheimer's disease (AD). One important enzyme involved in this mechanism is superoxide dismutase 2 (SOD2). The gene for this enzyme lies within a single haplotype block at 6q25.3, a region showing evidence for linkage to AD in a genome scan. We genotyped four single nucleotide polymorphisms (SNPs) in SOD2 in families of the National Institute of Mental Health-AD Genetics Initiative (ADGI): rs2758346 in the 5' untranslated region (UTR), rs4880 in exon 2, rs2855116 in intron 3 and rs5746136 in the 3'UTR. Under a dominant model, family-based association tests showed significant evidence for association of AD with the first three loci in a candidate gene set of families with individuals having age of onset of at least 50 years and two affected and one unaffected sibling, and in a late-onset subset of families (families with all affected individuals having age of onset of at least 65 years) from the full ADGI sample. The alleles transmitted more frequently to cases than expected under the null hypothesis were T, C, G, and G. Global tests of the transmission of haplotypes indicate that the first two loci have the most consistent association with risk of AD. Because of the high linkage disequilibrium in this small (14 kb) gene, and the presence of 100 SNPs in this gene, 26 of which may have functional significance, additional genotyping and sequencing are needed to identify the functionally relevant SNP. We discuss the importance of our findings and the relevance of SOD2 to AD risk. 相似文献
972.
Batrachochytrium dendrobatidis (Bd) is a fungus that can potentially lead to chytridiomycosis, an amphibian disease implicated in die-offs and population
declines in many regions of the world. Winter field surveys in the last decade have documented die-offs in populations of
the lowland leopard frog Rana yavapaiensis with chytridiomycosis. To test whether the fungus persists in host populations between episodes of observed host mortality,
we quantified field-based Bd infection rates during nonwinter months. We used PCR to sample for the presence of Bd in live
individuals from nine seemingly healthy populations of the lowland leopard frog as well as four of the American bullfrog R. catesbeiana (a putative vector for Bd) from Arizona. We found Bd in 10 of 13 sampled populations. The overall prevalence of Bd was 43%
in lowland leopard frogs and 18% in American bullfrogs. Our results suggest that Bd is widespread in Arizona during nonwinter
months and may become virulent only in winter in conjunction with other cofactors, or is now benign in these species. The
absence of Bd from two populations associated with thermal springs (water >30°C), despite its presence in nearby ambient waters,
suggests that these microhabitats represent refugia from Bd and chytridiomycosis. 相似文献
973.
Brigelius-Flohé R 《Genes & nutrition》2007,2(3):249-256
Observational studies with healthy persons demonstrated an inverse association of vitamin E with the risk of coronary heart disease or cancer, the outcome of large-scale clinical trials conducted to prove a benefit of vitamin E in the recurrence and/or progression of such disease, however, was disappointing. Vitamin E did not provide benefits to patients with cardiovascular diseases, cancer, diabetes or hypertension. Even harmful events and worsening of pre-existing diseases were reported, which are hard to explain. Since vitamin E is metabolized along the same routes as xenobiotics and induces drug-metabolizing enzymes in rodents, it is hypothesized that a supplementation with high dosages of vitamin E may also lead to an induction of the drug-metabolizing system in patients that depend on drug therapy. Compromising essential therapy might therefore outweigh any benefit of vitamin E in patients. It is recommended to work out at which threshold the drug-metabolizing system can be induced in humans before new trials with high dosages of vitamin E are started. 相似文献
974.
J. Kodde N. Hofman C. L. A. Reichert I. M. van Langen A. A. M. Wilde 《Netherlands heart journal》2007,15(12):412-414
BackgroundInherited heart disease is becoming a substantial part of everyday cardiology practice while genetic counselling still only takes place at university hospitals. In this study we review our seven-year experience with cardiogenetic counselling in a non-university hospital. MethodsRetrospective analysis of patient records. ResultsA total number of 83 index patients were counselled. In 65 patients DNA tests were performed, resulting in 26 positive tests. In all patients with genotype confirmation of hereditary cardiovascular disease and in 32 families without a molecular diagnosis, family screening was advised. Out of 120 subsequently tested family members, 47 molecular genetic diagnoses were confirmed. ConclusionAlthough the number of patients reviewed was small, our data show that cardiogenetic diseases are part of daily cardiology practice. We believe counselling should be performed in more general hospitals. This is an excellent opportunity for collaboration between university and nonuniversity hospitals, with immediate benefit for patients and their relatives. (Neth Heart J 2007;15: 412-4.) 相似文献
975.
Roest PA van Iperen L Vis S Wisse LJ Poelmann RE Steegers-Theunissen RP Molin DG Eriksson UJ Gittenberger-De Groot AC 《Birth defects research. Part A, Clinical and molecular teratology》2007,79(3):231-235
BACKGROUND: Diabetes mellitus during pregnancy increases the risk for congenital heart disease in the offspring. The majority of the cardiovascular malformations occur in the outflow tract and pharyngeal arch arteries, where neural crest cells are essential for normal development. We studied the effects of specific exposure of neural crest cells to elevated glucose on heart development. Antioxidants reduce the damaging effect of glucose on neural crest cells in vitro; therefore, we investigated the effect of supplementing N-acetylcysteine in vivo. METHODS: Cardiac neural crest of HH 8-12 chicken embryos was directly exposed by a single injection in the neural tube with 30 mM D-glucose (or 30 mM L-glucose as a control). To examine the effect of a reduction in oxidative stress, we added 2 mM N-acetylcysteine to the injected D-glucose. RESULTS: Exposure of neural crest cells to elevated D-glucose-induced congenital heart malformations in 82% of the embryos. In the embryos injected with L-glucose, only 9% developed a heart malformation. As expected, all malformations were located in the outflow tract and pharyngeal arch arteries. The frequency of heart malformations decreased from 82% to 27% when 2 mM N-acetylcysteine was added to the injected D-glucose. CONCLUSIONS: These data are the first to confirm that the vulnerability of neural crest cells to elevated glucose induces congenital heart malformations. The fact that N-acetylcysteine limits the teratogenicity of glucose implies that its damaging effect is mediated by an increase of oxidative stress in the neural crest cells. 相似文献
976.
Gardner BR Strickland MJ Correa A 《Birth defects research. Part A, Clinical and molecular teratology》2007,79(7):559-564
BACKGROUND: Although many birth defects surveillance programs incorporate georeferenced records into their databases, practical methods for routine spatial surveillance are lacking. We present a macroprogram written for the software package R designed for routine exploratory spatial analysis of birth defects data, the Automated Spatial Surveillance Program (ASSP), and present an application of this program using spina bifida prevalence data for metropolitan Atlanta. METHODS: Birth defects surveillance data were collected by the Metropolitan Atlanta Congenital Defects Program. We generated ASSP maps for two groups of years that correspond roughly to the periods before (1994-1998) and after (1999-2002) folic acid fortification of flour. ASSP maps display census tract-specific spina bifida prevalence, smoothed prevalence contours, and locations of statistically elevated prevalence. We used these maps to identify areas of elevated prevalence for spina bifida. RESULTS: We identified a large area of potential concern in the years following fortification of grains and cereals with folic acid. This area overlapped census tracts containing large numbers of Hispanic residents. CONCLUSIONS: The potential utility of ASSP for spatial disease monitoring was demonstrated by the identification of areas of high prevalence of spina bifida and may warrant further study and monitoring. We intend to further develop ASSP so that it becomes practical for routine spatial monitoring of birth defects. 相似文献
977.
Mark C. Derbyshire Toby E. Newman Yuphin Khentry Akeem Owolabi Taiwo 《Molecular Plant Pathology》2022,23(8):1075-1090
Sclerotinia sclerotiorum is a pathogenic fungus that infects hundreds of plant species, including many of the world's most important crops. Key features of S. sclerotiorum include its extraordinary host range, preference for dicotyledonous plants, relatively slow evolution, and production of protein effectors that are active in multiple host species. Plant resistance to this pathogen is highly complex, typically involving numerous polymorphisms with infinitesimally small effects, which makes resistance breeding a major challenge. Due to its economic significance, S. sclerotiorum has been subjected to a large amount of molecular and evolutionary research. In this updated pathogen profile, we review the evolutionary and molecular features of S. sclerotiorum and discuss avenues for future research into this important species. 相似文献
978.
Yuxuan Xi Véronique Chalvon André Padilla Stella Cesari Thomas Kroj 《Molecular Plant Pathology》2022,23(9):1320-1330
The rice nucleotide-binding (NB) and leucine-rich repeat (LRR) domain immune receptors (NLRs) RGA4 and RGA5 form a helper NLR/sensor NLR (hNLR/sNLR) pair that specifically recognizes the effectors AVR-Pia and AVR1-CO39 from the blast fungus Magnaporthe oryzae. While RGA4 contains only canonical NLR domains, RGA5 has an additional unconventional heavy metal-associated (HMA) domain integrated after its LRR domain. This RGA5HMA domain binds the effectors and is crucial for their recognition. Investigation of the three-dimensional structure of the AVR1-CO39/RGA5HMA complex by X-ray crystallography identified a candidate surface for effector binding in the HMA domain and showed that the HMA domain self-interacts in the absence of effector through the same surface. Here, we investigated the relevance of this HMA homodimerization for RGA5 function and the role of the RGA5HMA effector-binding and self-interaction surface in effector recognition. By analysing structure-informed point mutations in the RGA5HMA-binding surface in protein interaction studies and in Nicotiana benthamiana cell death assays, we found that HMA self-interaction does not contribute to RGA5 function. However, the effector-binding surface of RGA5HMA identified by X-ray crystallography is crucial for both in vitro and in vivo effector binding as well as effector recognition. These results support the current hypothesis that noncanonical integrated domains of NLRs act primarily as effector traps and deepen our understanding of the sNLRs' function within NLR pairs. 相似文献
979.
Traumatic exposures can affect beliefs and behaviors related to the spread of sexually transmitted diseases (STDs), a persistent public health problem. I leverage a natural experiment created by variation in US military deployment location assignments to estimate how combat exposure changes a surviving deployed male veteran’s probability of acquiring a sexually transmitted disease. I analyze longitudinal data from 1994 to 2008 on 485 deployed veterans with information theoretic methods to reduce the sensitivity of estimates to small samples, an infrequently observed outcome, and highly correlated covariates. For veterans assigned to a combat zone, I estimate combat exposure results in a 5.4 percentage point increase in the probability of acquiring an STD. Additional estimations provide evidence suggesting risky behaviors involving substance use or multiple sexual partners may serve as pathways from combat exposure to STDs. My results are relevant to discussions regarding STD screening and care needs for trauma exposed individuals. 相似文献
980.
We hypothesize that the impact of antibiotics is moderated by a population’s inherent (genetic) resistance to infectious disease. Using the introduction of sulfa drugs in 1937, we show that US states that are more genetically susceptible to infectious disease saw larger declines in their bacterial mortality rates following the introduction of sulfa drugs in 1937. This suggests area-level genetic endowments of disease resistance and the discovery of medical technologies have acted as substitutes in determining levels of health across the US. We also document immediate effects of sulfa drug exposure to the age of the workforce and cumulative effects on educational attainment for cohorts exposed to sulfa drugs in early life. 相似文献