全文获取类型
收费全文 | 8926篇 |
免费 | 771篇 |
国内免费 | 2篇 |
专业分类
9699篇 |
出版年
2024年 | 12篇 |
2023年 | 39篇 |
2022年 | 109篇 |
2021年 | 228篇 |
2020年 | 113篇 |
2019年 | 152篇 |
2018年 | 188篇 |
2017年 | 161篇 |
2016年 | 291篇 |
2015年 | 469篇 |
2014年 | 508篇 |
2013年 | 545篇 |
2012年 | 775篇 |
2011年 | 736篇 |
2010年 | 459篇 |
2009年 | 423篇 |
2008年 | 568篇 |
2007年 | 569篇 |
2006年 | 531篇 |
2005年 | 535篇 |
2004年 | 491篇 |
2003年 | 457篇 |
2002年 | 429篇 |
2001年 | 73篇 |
2000年 | 50篇 |
1999年 | 104篇 |
1998年 | 111篇 |
1997年 | 71篇 |
1996年 | 56篇 |
1995年 | 58篇 |
1994年 | 47篇 |
1993年 | 51篇 |
1992年 | 40篇 |
1991年 | 31篇 |
1990年 | 38篇 |
1989年 | 26篇 |
1988年 | 28篇 |
1987年 | 18篇 |
1986年 | 16篇 |
1985年 | 15篇 |
1984年 | 18篇 |
1983年 | 12篇 |
1982年 | 11篇 |
1981年 | 11篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1978年 | 6篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1974年 | 2篇 |
排序方式: 共有9699条查询结果,搜索用时 15 毫秒
41.
KLOTHO allele status and the risk of early-onset occult coronary artery disease 总被引:10,自引:0,他引:10 下载免费PDF全文
Arking DE Becker DM Yanek LR Fallin D Judge DP Moy TF Becker LC Dietz HC 《American journal of human genetics》2003,72(5):1154-1161
We previously identified a functional variant of KLOTHO (termed "KL-VS"), which harbors two amino acid substitutions in complete linkage disequilibrium and is associated with reduced human longevity when in homozygosity. Klotho-deficient mice display extensive arteriosclerosis when fed a normal diet, suggesting a potent genetic predisposition. To determine whether klotho influences atherosclerotic risk in humans, we performed cross-sectional studies to assess the association between the KL-VS allele and occult coronary artery disease (CAD) in two independent samples of apparently healthy siblings of individuals with early-onset (age <60 years) CAD (SIBS-I [N=520] and SIBS-II [N=436]). Occult CAD was defined as the occurrence of a reversible perfusion defect during exercise thallium scintigraphy and/or as an abnormal result of an exercise electrocardiogram (SIBS-I, n=97; SIBS-II, n=56). In SIBS-I, the KL-VS allele conferred a relative odds of 1.90 (95% confidence interval 1.21-2.98) for occult CAD, after adjusting for familial intraclass correlations (P<.005). Logistic regression modeling, incorporating known CAD risk factors, demonstrated that the KL-VS allele is an independent risk factor (P<.019) and that the imposed risk of KL-VS allele status is influenced by modifiable risk factors. Hypertension (P<.022) and increasing high-density lipoprotein cholesterol (HDL-C) levels (P<.022) mask or reduce the risk conferred by the KL-VS allele, respectively, whereas current smoking (P<.004) increases the risk. Remarkably concordant effects of the KL-VS allele and modifying factors on the risk of occult CAD were seen in SIBS-II. These results demonstrate that the KL-VS allele is an independent risk factor for occult CAD in two independent high-risk samples. Modifiable risk factors, including hypertension, smoking status, and HDL-C level, appear to influence the risk imposed by this allele. 相似文献
42.
Lisa M. Stout Ruth E. Blake James P. Greenwood Anna M. Martini & Eben C. Rose 《FEMS microbiology ecology》2009,70(3):70-80
The volcanic Sulphur Springs, St. Lucia, present an extreme environment due to high temperatures, low pH values, and high concentrations of sulfate and boron. St. Lucia offers some unique geochemical characteristics that may shape the microbial communities within the Sulphur Springs area. We chose six pools representing a range of geochemical characteristics for detailed microbial community analyses. Chemical concentrations varied greatly between sites. Microbial diversity was analyzed using 16S rRNA gene clone library analyses. With the exception of one pool with relatively low concentrations of dissolved ions, microbial diversity was very low, with Aquificales sequences dominating bacterial communities at most pools. The archaeal component of all pools was almost exclusively Acidianus spp. and did not vary between sites with different chemical characteristics. In the pool with the highest boron and sulfate concentrations, only archaeal sequences were detected. Compared with other sulfur springs such as those at Yellowstone, the microbial diversity at St. Lucia is very different, but it is similar to that at the nearby Lesser Antilles island of Montserrat. While high elemental concentrations seem to be related to differences in bacterial diversity here, similarities with other Lesser Antilles sites suggest that there may be a biogeographical component as well. 相似文献
43.
Sarah?E.?TurnerEmail author Lisa?Gould David?A.?Duffus 《International journal of primatology》2005,26(6):1435-1457
We studied the relationship between maternal behavior and infant disability in 12 mother-infant dyads for the first 5 weeks
of infant life in the free-ranging Japanese macaque (Macaca fuscata) group on Awaji Island, Japan, from May to September 2001. Congenital limb malformations are prevalent in this population,
and as such carry implications for behavior and conservation. We did not detect any differences in maternal activity budgets,
mother-infant physical contact, infant holding, and overall nursing and infant transport time between mothers of non-disabled
infants, disabled infants that were able to cling to their mothers, and disabled infants whose limb structure prevented clinging.
Mothers of infants with limb malformations severe enough to prevent normal clinging behavior manually supported their infants
during nursing and locomotion significantly more than other mothers did theirs. Increased support-carrying and support-nursing,
and higher frequencies of holding the infant to one's ventrum, suggest that mothers of extensively malformed infants may be
investing more to facilitate the survival of their offspring and that infant disability appears to be influencing maternal
behaviors in this population. 相似文献
44.
Miller LM Wang Q Telivala TP Smith RJ Lanzirotti A Miklossy J 《Journal of structural biology》2006,155(1):30-37
Alzheimer's disease (AD) is characterized by the misfolding and plaque-like accumulation of a naturally occurring peptide in the brain called amyloid beta (Abeta). Recently, this process has been associated with the binding of metal ions such as iron (Fe), copper (Cu), and zinc (Zn). It is thought that metal dyshomeostasis is involved in protein misfolding and may lead to oxidative stress and neuronal damage. However, the exact role of the misfolded proteins and metal ions in the degenerative process of AD is not yet clear. In this study, we used synchrotron Fourier transform infrared micro-spectroscopy (FTIRM) to image the in situ secondary structure of the amyloid plaques in brain tissue of AD patients. These results were spatially correlated with metal ion accumulation in the same tissue sample using synchrotron X-ray fluorescence (SXRF) microprobe. For both techniques, a spatial resolution of 5-10 microm was achieved. FTIRM results showed that the amyloid plaques have elevated beta-sheet content, as demonstrated by a strong amide I absorbance at 1625cm(-1). Using SXRF microprobe, we find that AD tissue also contains "hot spots" of accumulated metal ions, specifically Cu and Zn, with a strong spatial correlation between these two ions. The "hot spots" of accumulated Zn and Cu were co-localized with beta-amyloid plaques. Thus for the first time, a strong spatial correlation has been observed between elevated beta-sheet content in Abeta plaques and accumulated Cu and Zn ions, emphasizing an association of metal ions with amyloid formation in AD. 相似文献
45.
Mudhasani R Zhu Z Hutvagner G Eischen CM Lyle S Hall LL Lawrence JB Imbalzano AN Jones SN 《The Journal of cell biology》2008,181(7):1055-1063
Dicer, an enzyme involved in microRNA (miRNA) maturation, is required for proper cell differentiation and embryogenesis in mammals. Recent evidence indicates that Dicer and miRNA may also regulate tumorigenesis. To better characterize the role of miRNA in primary cell growth, we generated Dicer-conditional mice. Ablation of Dicer and loss of mature miRNAs in embryonic fibroblasts up-regulated p19(Arf) and p53 levels, inhibited cell proliferation, and induced a premature senescence phenotype that was also observed in vivo after Dicer ablation in the developing limb and in adult skin. Furthermore, deletion of the Ink4a/Arf or p53 locus could rescue fibroblasts from premature senescence induced by Dicer ablation. Although levels of Ras and Myc oncoproteins appeared unaltered, loss of Dicer resulted in increased DNA damage and p53 activity in these cells. These results reveal that loss of miRNA biogenesis activates a DNA damage checkpoint, up-regulates p19(Arf)-p53 signaling, and induces senescence in primary cells. 相似文献
46.
Tsang TM Annis DS Kronshage M Fenno JT Usselman LD Mosher DF Krukonis ES 《The Journal of biological chemistry》2012,287(20):16759-16767
The Yersinia pestis adhesin molecule Ail interacts with the extracellular matrix protein fibronectin (Fn) on host cells to facilitate efficient delivery of cytotoxic Yop proteins, a process essential for plague virulence. A number of bacterial pathogens are known to bind to the N-terminal region of Fn, comprising type I Fn (FNI) repeats. Using proteolytically generated Fn fragments and purified recombinant Fn fragments, we demonstrated that Ail binds the centrally located 120-kDa fragment containing type III Fn (FNIII) repeats. A panel of monoclonal antibodies (mAbs) that recognize specific epitopes within the 120-kDa fragment demonstrated that mAb binding to (9)FNIII blocks Ail-mediated bacterial binding to Fn. Epitopes of three mAbs that blocked Ail binding to Fn were mapped to a similar face of (9)FNIII. Antibodies directed against (9)FNIII also inhibited Ail-dependent cell binding activity, thus demonstrating the biological relevance of this Ail binding region on Fn. Bacteria expressing Ail on their surface could also bind a minimal fragment of Fn containing repeats (9-10)FNIII, and this binding was blocked by a mAb specific for (9)FNIII. These data demonstrate that Ail binds to (9)FNIII of Fn and presents Fn to host cells to facilitate cell binding and delivery of Yops (cytotoxins of Y. pestis), a novel interaction, distinct from other bacterial Fn-binding proteins. 相似文献
47.
48.
Determining the importance of stopover and staging areas to migrating shorebirds (Aves: Charadriiformes) is essential if such habitats are to be successfully protected. Migration chronology, species composition, length of stay, body condition, and estimated total abundance of shorebirds during spring and fall migratory periods of 2008 and 2009 were documented on Akimiski Island, Nunavut, Canada. Fourteen shorebird species were observed during spring point counts and 18 during fall. Semipalmated (Calidris pusilla) and White-rumped (C. fuscicollis) Sandpipers comprised about 80?% of all individuals observed. A greater number of species and individuals were observed during fall than spring in both years. Radio-transmitters attached to juvenile Semipalmated and Least (C. minutilla) Sandpipers indicated highly variable lengths of stay ranging up to 26?days in both species (Semipalmated Sandpiper averaged 6.5?±?2.67?days, n?=?12; Least Sandpipers averaged 7.25?±?3.79?days, n?=?8). In 2009, Semipalmated Sandpipers captured and weighed later in the season were significantly heavier than those captured earlier suggesting that this species is refueling while on Akimiski Island. A fall migration seasonal density of 5,267 (2,193–8,341) shorebirds/km2 was estimated given a residence probability (i.e., the probability of an individual being present in consecutive counts) of 0.906?±?0.181. Assuming similar habitat value and shorebird density, an extrapolation of the seasonal plot density of 5,267 birds/km2 to the total 192?km2 mudflat habitat on Akimiski Island yields an estimate of 1,011,264 (421,098–1,601,429) shorebirds during fall migration, making Akimiski Island of Hemispheric importance as a staging site for migrant arctic-breeding shorebirds. 相似文献
49.
Sarah A. Cocherell Stephanie N. Chun Dennis E. Cocherell Lisa C. Thompson A. Peter Klimley Joseph J. CechJr. 《Environmental Biology of Fishes》2012,93(1):143-150
In regulated rivers, fluctuating water depths associated with pulsed discharges may strand small fish in side channels and
pools. Quantitative assessments of stranded fish are difficult in field studies (e.g., due to unknown effects of avian and
terrestrial vertebrate predators). To assess such lateral displacement and stranding on juvenile stream fishes, we designed,
constructed, and tested (with three species) a 2 × 1-m, lateral-displacement flume. The flume featured a main channel that
never drained and a raised, wide “floodplain” channel that alternately flooded, with a simulated pulse, and became dewatered.
The floodplain contained four pools, with different shapes and draining capacities, in which fish could become stranded as
the water level subsided. Fish-stranding rates (8%) in this relatively compact laboratory flume, after exposure to simulated
pulsed stream flows, were comparable to those observed in past investigations using larger, artificial streams. 相似文献
50.
Van Bergen NJ Crowston JG Kearns LS Staffieri SE Hewitt AW Cohn AC Mackey DA Trounce IA 《PloS one》2011,6(6):e21347
Autosomal Dominant Optic Atrophy (ADOA) is the most common inherited optic atrophy where vision impairment results from specific loss of retinal ganglion cells of the optic nerve. Around 60% of ADOA cases are linked to mutations in the OPA1 gene. OPA1 is a fission-fusion protein involved in mitochondrial inner membrane remodelling. ADOA presents with marked variation in clinical phenotype and varying degrees of vision loss, even among siblings carrying identical mutations in OPA1. To determine whether the degree of vision loss is associated with the level of mitochondrial impairment, we examined mitochondrial function in lymphoblast cell lines obtained from six large Australian OPA1-linked ADOA pedigrees. Comparing patients with severe vision loss (visual acuity [VA]<6/36) and patients with relatively preserved vision (VA>6/9) a clear defect in mitochondrial ATP synthesis and reduced respiration rates were observed in patients with poor vision. In addition, oxidative phosphorylation (OXPHOS) enzymology in ADOA patients with normal vision revealed increased complex II+III activity and levels of complex IV protein. These data suggest that OPA1 deficiency impairs OXPHOS efficiency, but compensation through increases in the distal complexes of the respiratory chain may preserve mitochondrial ATP production in patients who maintain normal vision. Identification of genetic variants that enable this response may provide novel therapeutic insights into OXPHOS compensation for preventing vision loss in optic neuropathies. 相似文献