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排序方式: 共有1122条查询结果,搜索用时 156 毫秒
91.
Kevin M. Waters Daniel O. Stram Mohamed T. Hassanein Lo?c Le Marchand Lynne R. Wilkens Gertraud Maskarinec Kristine R. Monroe Laurence N. Kolonel David Altshuler Brian E. Henderson Christopher A. Haiman 《PLoS genetics》2010,6(8)
It has been recently hypothesized that many of the signals detected in genome-wide association studies (GWAS) to T2D and other diseases, despite being observed to common variants, might in fact result from causal mutations that are rare. One prediction of this hypothesis is that the allelic associations should be population-specific, as the causal mutations arose after the migrations that established different populations around the world. We selected 19 common variants found to be reproducibly associated to T2D risk in European populations and studied them in a large multiethnic case-control study (6,142 cases and 7,403 controls) among men and women from 5 racial/ethnic groups (European Americans, African Americans, Latinos, Japanese Americans, and Native Hawaiians). In analysis pooled across ethnic groups, the allelic associations were in the same direction as the original report for all 19 variants, and 14 of the 19 were significantly associated with risk. In summing the number of risk alleles for each individual, the per-allele associations were highly statistically significant (P<10−4) and similar in all populations (odds ratios 1.09–1.12) except in Japanese Americans the estimated effect per allele was larger than in the other populations (1.20; Phet = 3.8×10−4). We did not observe ethnic differences in the distribution of risk that would explain the increased prevalence of type 2 diabetes in these groups as compared to European Americans. The consistency of allelic associations in diverse racial/ethnic groups is not predicted under the hypothesis of Goldstein regarding “synthetic associations” of rare mutations in T2D. 相似文献
92.
Todd J. Brinkman Michael K. Schwartz David K. Person Kristine L. Pilgrim Kris J. Hundertmark 《Conservation Genetics》2010,11(4):1547-1552
Non-invasive wildlife research using DNA from feces has become increasingly popular. Recent studies have attempted to solve
problems associated with recovering DNA from feces by investigating the influence of factors such as season, diet, collection
method, preservation method, extraction protocol, and time. To our knowledge, studies of this nature have not addressed DNA
degradation over time in wet environments, and have not been performed on fecal pellets of ungulates. Therefore, our objective
was to determine the length of time a fecal pellet from a Sitka black-tailed deer (Odocoileus hemionus sitkensis) could remain in the field in a temperate rainforest environment before the DNA became too degraded for individual identification.
Pellets were extracted from the rectum of recently killed deer and placed in an environment protected from rainfall and in
an environment exposed to rainfall. Pellets from each treatment group were sampled at intervals of 2, 7, 14, 21, and 28 days
after deer harvest. DNA was extracted from sampled pellets and individual samples were genotyped using microsatellite markers.
Amplification failure and errors (dropout and false alleles) were recorded to determine extent of DNA degradation. Eighty
percent of samples in the protected environment and 22% of samples in the exposed environment were successfully genotyped
during the 28-day experiment. With no samples being successfully genotyped in the exposed environment after 7 days, our study
showed that rainfall significantly increases degradation rates of DNA from ungulate pellets. 相似文献
93.
94.
Michael Hillstrom Timothy D. Meehan Kristine Kelly Richard L. Lindroth 《Plant and Soil》2010,336(1-2):75-85
Elevated CO2 and O3 alter tree quality and the quality of herbivore inputs, such as frass, to forest soil. Altered quality or quantity of herbivore inputs to the forest floor can have large impacts on belowground processes. We collected green leaves and frass from whitemarked tussock moth caterpillars from aspen-birch stands at the Aspen Free Air CO2 Enrichment (FACE) site near Rhinelander, WI, USA. Small or large quantities of frass, greenfall, or a 1:1 ratio of frass and greenfall were added to microcosms for each FACE treatment (control, +CO2, +O3, +CO2+O3). We measured initial frass and greenfall quality, and recorded microbial respiration, and nitrate leaching over 40 days. Elevated carbon dioxide (eCO2) and tropospheric ozone (eO3) significantly altered the carbon, nitrogen, and condensed tannin content of insect frass and green leaves. Although FACE treatments affected input quality, they had minimal effect on microbial respiration and no effect on nitrogen leaching. In contrast, input quantity substantially influenced microbial respiration and nitrate leaching. Respiratory carbon loss and nitrate immobilization were nearly double in microcosms receiving large amounts of herbivore inputs than those receiving no herbivore inputs. Small amounts of herbivore inputs, however, did not significantly alter microbial respiration or immobilization, suggesting that effects of herbivore inputs on soil processes will be detected only at moderate to high herbivory/input levels. These results suggest that subtle changes in frass and greenfall quality may not affect soil nutrient cycling. In contrast, environmental change induced increases in insect population size or frass and greenfall inputs to the soil may substantially impact nutrient cycling. 相似文献
95.
The field of tissue engineering has made considerable strides since it was first described in the late 1980s. The advent and subsequent boom in stem cell biology, emergence of novel technologies for biomaterial development and further understanding of developmental biology have contributed to this accelerated progress. However, continued efforts to translate tissue-engineering strategies into clinical therapies have been hampered by the problems associated with scaling up laboratory methods to produce large, complex tissues. The significant challenges faced by tissue engineers include the production of an intact vasculature within a tissue-engineered construct and recapitulation of the size and complexity of a whole organ. Here we review the basic components necessary for bioengineering organs-biomaterials, cells and bioactive molecules-and discuss various approaches for augmenting these principles to achieve organ level tissue engineering. Ultimately, the successful translation of tissue-engineered constructs into everyday clinical practice will depend upon the ability of the tissue engineer to "scale up" every aspect of the research and development process. 相似文献
96.
Hansen L Hare KJ Hartmann B Deacon CF Ugleholdt RK Plamboeck A Holst JJ 《Regulatory peptides》2007,138(2-3):126-132
Little is known about the metabolism of the intestinotropic factor glucagon-like peptide-2 (GLP-2); except that it is a substrate for dipeptidyl peptidase IV (DPP-IV) and that it appears to be eliminated by the kidneys. We, therefore, investigated GLP-2 metabolism in six multicatheterized pigs receiving intravenous GLP-2 infusions (2 pmol/kg/min) before and after administration of valine-pyrrolidide (300 mumol/kg; a well characterized DPP-IV inhibitor). Plasma samples were analyzed by radioimmunoassays allowing determination of intact, biologically active GLP-2 and the DPP-IV metabolite GLP-2 (3-33). During infusion of GLP-2 alone, 30.9+/-1.7% of the infused peptide was degraded to GLP-2 (3-33). After valine-pyrrolidide, there was no significant formation of the metabolite. Significant extraction of intact GLP-2 was observed across the kidneys, the extremities (represented by a leg), and the splanchnic bed, resulting in a metabolic clearance rate (MCR) of 6.80+/-0.47 ml/kg/min and a plasma half-life of 6.8+/-0.8 min. Hepatic extraction was not detected. Valine-pyrrolidide addition did not affect extraction ratios significantly, but decreased (p=0.003) MCR to 4.18+/-0.27 ml/kg/min and increased (p=0.052) plasma half-life to 9.9+/-0.8 min. The metabolite was eliminated with a half-life of 22.1+/-2.6 min and a clearance of 2.07+/-0.11 ml/kg/min. In conclusion, intact GLP-2 is eliminated in the peripheral tissues, the splanchnic bed and the kidneys, but not in the liver, by mechanisms unrelated to DPP-IV. However, DPP-IV is involved in the overall GLP-2 metabolism and seems to be the sole enzyme responsible for N-terminal degradation of GLP-2. 相似文献
97.
Adams WW Watson AM Mueh KE Amiard V Turgeon R Ebbert V Logan BA Combs AF Demmig-Adams B 《Photosynthesis research》2007,94(2-3):455-466
The potential role of foliar carbon export features in the acclimation of photosynthetic capacity to differences and changes
in light environment was evaluated. These features included apoplastic vs. symplastic phloem loading, density of loading veins,
plasmodesmatal frequency in intermediary cells, and the ratio of loading cells to sieve elements. In initial studies, three
apoplastic loaders (spinach, pea, Arabidopsis thaliana) exhibited a completely flexible photosynthetic response to changing light conditions, while two symplastic loaders (pumpkin,
Verbascum phoeniceum), although able to adjust to different long-term growth conditions, were more limited in their response when transferred
from low (LL) to high (HL) light. This suggested that constraints imposed by the completely physical pathway of sugar export
might act as a bottleneck in the export of carbon from LL-acclimated leaves of symplastic loaders. While both symplastic loaders
exhibited variable loading vein densities (low in LL and high in HL), none of the three apoplastic loaders initially characterized
exhibited such differences. However, an additional apoplastic species (tomato) exhibited similar differences in vein density
during continuous growth in different light environments. Furthermore, in contrast to the other apoplastic loaders, photosynthetic
acclimation in tomato was not complete following a transfer from LL to HL. This suggests that loading vein density and loading
cells per sieve element, and thus apparent loading surface capacity, play a major role in the potential for photosynthetic
acclimation to changes in light environment. Photosynthetic acclimation and vein density acclimation were also characterized
in the slow-growing, sclerophytic evergreen Monstera deliciosa. This evergreen possessed a lower vein density during growth in LL compared to HL and exhibited a more severely limited potential
for photosynthetic acclimation to increases in light environment than the rapidly-growing, mesophytic annuals. 相似文献
98.
Defects in genes that control DNA repair, proliferation, and apoptosis can increase genomic instability, and thus promote malignant progression. Although most tumors that arise in humans with neurofibromatosis type 1 (NF1) are benign, these individuals are at increased risk for malignant peripheral nerve sheath tumors (MPNST). To characterize additional mutations required for the development of MPNST from benign plexiform neurofibromas, we generated a mouse model for these tumors by combining targeted null mutations in Nf1 and p53, in cis. CisNf1+/-; p53+/- mice spontaneously develop PNST, and these tumors exhibit loss-of-heterozygosity at both the Nf1 and p53 loci. Because p53 has well-characterized roles in the DNA damage response, DNA repair, and apoptosis, and because DNA repair genes have been proposed to act as modifiers in NF1, we used the cisNf1+/-; p53+/- mice to determine whether a mutator phenotype arises in NF1-associated malignancies. To quantitate spontaneous mutant frequencies (MF), we crossed the Big Blue mouse, which harbors a lacI transgene, to the cisNf1+/-; p53+/- mice, and isolated genomic DNA from both tumor and normal tissues in compound heterozygotes and wild-type siblings. Many of the PNST exhibited increased mutant frequencies (MF=4.70) when compared to normal peripheral nerve and brain (MF=2.09); mutations occurred throughout the entire lacI gene, and included base substitutions, insertions, and deletions. Moreover, the brains, spleens, and livers of these cisNf1+/-; p53+/- animals exhibited increased mutant frequencies when compared to tissues from wild-type littermates. We conclude that a mild mutator phenotype arises in the tumors and tissues of cisNf1+/-; p53+/- mice, and propose that genomic instability influences NF1 tumor progression and disease severity. 相似文献
99.
Castellano JM Batrynchuk J Dolbeare K Verma V Mann A Skoblenick KJ Johnson RL Mishra RK 《Peptides》2007,28(10):2009-2015
Two melanocyte-stimulating hormone release inhibiting factor-1 (MIF-1) also known as L-prolyl-L-leucyl-glycinamide (PLG) peptidomimetic analogs, 3(R)-[[[2(S)-pyrrolidinyl]carbonyl]-amino]-3-(butyl)-2-oxo-1-pyrrolidineacetamide trifluoroacetate (A) and 3(R)-[[[2(S)-pyrrolidinyl]carbonyl]amino]-3-(benzyl)-2-oxo-1-pyrrolidineacetamide trifluoroacetate (B), were evaluated for their ability to modulate dopaminergic activity by measuring apomorphine-induced rotations in 6-hydroxydopamine (6-OHDA)-lesioned rats, and haloperidol (HP)-induced vacuous chewing movements (VCMs) in rats; animal models of Parkinson's disease (PD) and human tardive dyskinesia (TD), respectively. In the 6-OHDA model, both analogs were found to potentiate the contralateral rotational behavior induced by apomorphine dose-dependently and with approximately the same potency. Furthermore, each analog was able to significantly attenuate HP-induced VCMs with almost equal efficacy. The potency and efficacy of these analogs were significantly greater than their parent compound, PLG. These results suggest that both analogs can modulate dopaminergic activity in vivo, likely by the same mechanisms recruited by PLG previously reported. 相似文献
100.