全文获取类型
收费全文 | 14485篇 |
免费 | 1257篇 |
国内免费 | 5篇 |
专业分类
15747篇 |
出版年
2023年 | 48篇 |
2022年 | 105篇 |
2021年 | 228篇 |
2020年 | 113篇 |
2019年 | 184篇 |
2018年 | 195篇 |
2017年 | 174篇 |
2016年 | 382篇 |
2015年 | 581篇 |
2014年 | 757篇 |
2013年 | 865篇 |
2012年 | 1097篇 |
2011年 | 1075篇 |
2010年 | 709篇 |
2009年 | 631篇 |
2008年 | 902篇 |
2007年 | 872篇 |
2006年 | 841篇 |
2005年 | 769篇 |
2004年 | 748篇 |
2003年 | 758篇 |
2002年 | 704篇 |
2001年 | 145篇 |
2000年 | 139篇 |
1999年 | 169篇 |
1998年 | 222篇 |
1997年 | 147篇 |
1996年 | 126篇 |
1995年 | 144篇 |
1994年 | 115篇 |
1993年 | 134篇 |
1992年 | 137篇 |
1991年 | 99篇 |
1990年 | 87篇 |
1989年 | 82篇 |
1988年 | 71篇 |
1987年 | 55篇 |
1986年 | 74篇 |
1985年 | 69篇 |
1984年 | 84篇 |
1983年 | 48篇 |
1982年 | 65篇 |
1981年 | 50篇 |
1980年 | 45篇 |
1979年 | 53篇 |
1978年 | 41篇 |
1977年 | 54篇 |
1976年 | 36篇 |
1974年 | 41篇 |
1973年 | 43篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
181.
Michael D.C. Evans Christine Hudon Ervin B. Podgorsak Carolyn R. Freeman 《Reports of Practical Oncology and Radiotherapy》2014,19(2):120-134
Total skin electron irradiation (TSEI) for patients with cutaneous lymphomas is technically challenging, and numerous approaches have been developed to overcome the many field matching problems associated with such a large and complex treatment volume. Since 1981 we have delivered TSEI using a rotational total skin electron irradiation (RTSEI) technique in conjunction with patch, treat and boost fields in order to provide complete skin and dose coverage. Initially we used a 6 MeV electron beam at an extended source-skin distance (SSD) on a modified linear accelerator. More recently we began using a high dose rate electron mode on a commercially available linear accelerator. The RTSEI technique allows the delivery of a seamless surface dose to the majority of the patient''s skin surface in a single treatment. In this review paper we present our three-decade experience with the technical development, dosimetry, treatment delivery and clinical outcomes of our RTSEI technique. 相似文献
182.
Christine Ewers‐Saucedo James M. Pringle Hector H. Sepúlveda James E. Byers Sergio A. Navarrete John P. Wares 《Ecology and evolution》2016,6(13):4403-4420
Dispersal and adaptation are the two primary mechanisms that set the range distributions for a population or species. As such, understanding how these mechanisms interact in marine organisms in particular – with capacity for long‐range dispersal and a poor understanding of what selective environments species are responding to – can provide useful insights for the exploration of biogeographic patterns. Previously, the barnacle Notochthamalus scabrosus has revealed two evolutionarily distinct lineages with a joint distribution that suggests an association with one of the two major biogeographic boundaries (~30°S) along the coast of Chile. However, spatial and genomic sampling of this system has been limited until now. We hypothesized that given the strong oceanographic and environmental shifts associated with the other major biogeographic boundary (~42°S) for Chilean coastal invertebrates, the southern mitochondrial lineage would dominate or go to fixation in locations further to the south. We also evaluated nuclear polymorphism data from 130 single nucleotide polymorphisms to evaluate the concordance of the signal from the nuclear genome with that of the mitochondrial sample. Through the application of standard population genetic approaches along with a Lagrangian ocean connectivity model, we describe the codistribution of these lineages through a simultaneous evaluation of coastal lineage frequencies, an approximation of larval behavior, and current‐driven dispersal. Our results show that this pattern could not persist without the two lineages having distinct environmental optima. We suggest that a more thorough integration of larval dynamics, explicit dispersal models, and near‐shore environmental analysis can explain much of the coastal biogeography of Chile. 相似文献
183.
Christine Driller Stefan Merker Dyah Perwitasari-Farajallah Walberto Sinaga Novita Anggraeni Hans Zischler 《PloS one》2015,10(11)
The Indonesian island of Sulawesi harbors a highly endemic and diverse fauna sparking fascination since long before Wallace’s contemplation of biogeographical patterns in the region. Allopatric diversification driven by geological or climatic processes has been identified as the main mechanism shaping present faunal distribution on the island. There is both consensus and conflict among range patterns of terrestrial species pointing to the different effects of vicariant events on once co-distributed taxa. Tarsiers, small nocturnal primates with possible evidence of an Eocene fossil record on the Asian mainland, are at present exclusively found in insular Southeast Asia. Sulawesi is hotspot of tarsier diversity, whereby island colonization and subsequent radiation of this old endemic primate lineage remained largely enigmatic. To resolve the phylogeographic history of Sulawesi tarsiers we analyzed an island-wide sample for a set of five approved autosomal phylogenetic markers (ABCA1, ADORA3, AXIN1, RAG1, and TTR) and the paternally inherited SRY gene. We constructed ML and Bayesian phylogenetic trees and estimated divergence times between tarsier populations. We found that their arrival at the Proto-Sulawesi archipelago coincided with initial Miocene tectonic uplift and hypothesize that tarsiers dispersed over the region in distinct waves. Intra-island diversification was spurred by land emergence and a rapid succession of glacial cycles during the Plio-Pleistocene. Some tarsier range boundaries concur with spatial limits in other taxa backing the notion of centers of faunal endemism on Sulawesi. This congruence, however, has partially been superimposed by taxon-specific dispersal patterns. 相似文献
184.
Evolutionary rescue by compensatory mutations is constrained by genomic and environmental backgrounds 下载免费PDF全文
Marie Filteau Véronique Hamel Marie‐Christine Pouliot Isabelle Gagnon‐Arsenault Alexandre K Dubé Christian R Landry 《Molecular systems biology》2015,11(10)
Since deleterious mutations may be rescued by secondary mutations during evolution, compensatory evolution could identify genetic solutions leading to therapeutic targets. Here, we tested this hypothesis and examined whether these solutions would be universal or would need to be adapted to one's genetic and environmental makeups. We performed experimental evolutionary rescue in a yeast disease model for the Wiskott–Aldrich syndrome in two genetic backgrounds and carbon sources. We found that multiple aspects of the evolutionary rescue outcome depend on the genotype, the environment, or a combination thereof. Specifically, the compensatory mutation rate and type, the molecular rescue mechanism, the genetic target, and the associated fitness cost varied across contexts. The course of compensatory evolution is therefore highly contingent on the initial conditions in which the deleterious mutation occurs. In addition, these results reveal biologically favored therapeutic targets for the Wiskott–Aldrich syndrome, including the target of an unrelated clinically approved drug. Our results experimentally illustrate the importance of epistasis and environmental evolutionary constraints that shape the adaptive landscape and evolutionary rate of molecular networks. 相似文献
185.
Viswanathan Rajagopalan Youhua Zhang Kaie Ojamaa Yue-feng Chen Alessandro Pingitore Christine J. Pol Debra Saunders Krithika Balasubramanian Rheal A. Towner A. Martin Gerdes 《PloS one》2016,11(3)
Background
A large body of evidence suggests that thyroid hormones (THs) are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3) treatment in myocardial infarction (MI) rats increased left ventricular (LV) contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI.Methods and Results
Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 μg/kg/day) was available in drinking water ad libitum immediately following MI and continuing for 2 month(s) (mo). Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy.Conclusions
Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans. 相似文献186.
Fabiana Dal Pozzo Bénédicte Renaville Ludovic Martinelle Robert Renaville Christine Thys Fran?ois Smeets Nathalie Kirschvink Fabien Grégoire Laurent Delooz Guy Czaplicki Claude Saegerman 《Applied and environmental microbiology》2016,82(1):81-86
The genotypic characterization of Coxiella burnetii provides useful information about the strains circulating at the farm, region, or country level and may be used to identify the source of infection for animals and humans. The aim of the present study was to investigate the strains of C. burnetii circulating in caprine and bovine Belgian farms using a single nucleotide polymorphism (SNP) technique. Direct genotyping was applied to different samples (bulk tank milk, individual milk, vaginal swab, fetal product, and air sample). Besides the well-known SNP genotypes, unreported ones were found in bovine and caprine samples, increasing the variability of the strains found in the two species in Belgium. Moreover, multiple genotypes were detected contemporarily in caprine farms at different years of sampling and by using different samples. Interestingly, certain SNP genotypes were detected in both bovine and caprine samples, raising the question of interspecies transmission of the pathogen. 相似文献
187.
Christine Neslund-Dudas Ashoka Kandegedara Oleksandr N. Kryvenko Nilesh Gupta Craig Rogers Benjamin A. Rybicki Q. Ping Dou Bharati Mitra 《Biological trace element research》2014,157(2):107-112
Although smoking is not associated with prostate cancer risk overall, smoking is associated with prostate cancer recurrence and mortality. Increased cadmium (Cd) exposure from smoking may play a role in progression of the disease. In this study, inductively coupled plasma mass spectrometry was used to determine Cd, arsenic (As), lead (Pb), and zinc (Zn) levels in formalin-fixed paraffin embedded tumor and tumor-adjacent non-neoplastic tissue of never- and ever-smokers with prostate cancer. In smokers, metal levels were also evaluated with regard to biochemical and distant recurrence of disease. Smokers (N?=?25) had significantly higher Cd (median ppb, p?=?0.03) and lower Zn (p?=?0.002) in non-neoplastic tissue than never-smokers (N?=?21). Metal levels were not significantly different in tumor tissue of smokers and non-smokers. Among smokers, Cd level did not differ by recurrence status. However, the ratio of Cd ppb to Pb ppb was significantly higher in both tumor and adjacent tissue of cases with distant recurrence when compared with cases without distant recurrence (tumor tissue Cd/Pb, 6.36 vs. 1.19, p?=?0.009, adjacent non-neoplastic tissue Cd/Pb, 6.36 vs. 1.02, p?=?0.038). Tissue Zn levels were also higher in smokers with distant recurrence (tumor, p?=?0.039 and adjacent non-neoplastic, p?=?0.028). These initial findings suggest that prostate tissue metal levels may differ in smokers with and without recurrence. If these findings are confirmed in larger studies, additional work will be needed to determine whether variations in metal levels are drivers of disease progression or are simply passengers of the disease process. 相似文献
188.
Sources of nitrate in rivers draining sixteen watersheds in the northeastern U.S.: Isotopic constraints 总被引:3,自引:4,他引:3
Mayer Bernhard Boyer Elizabeth W. Goodale Christine Jaworski Norbert A. van Breemen Nico Howarth Robert W. Seitzinger Sybil Billen Gilles Lajtha Kate Nadelhoffer Knute Van Dam Douwe Hetling Leo J. Nosal Miloslav Paustian Keith 《Biogeochemistry》2002,(1):171-197
The feasibility of using nitrogen and oxygenisotope ratios of nitrate (NO3
–) forelucidating sources and transformations ofriverine nitrate was evaluated in a comparativestudy of 16 watersheds in the northeastern U.S.A. Stream water was sampled repeatedly at theoutlets of the watersheds between January andDecember 1999 for determining concentrations,15N values, and 18Ovalues of riverine nitrate.In conjunction with information about land useand nitrogen fluxes,15Nnitrate and18Onitrate values providedmainly information about sources of riverinenitrate. In predominantly forested watersheds,riverine nitrate had mean concentrations ofless than 0.4 mg NO3
–-N L–1,15Nnitrate values of lessthan +5, and 18Onitratevalues between +12 and +19. This indicatesthat riverine nitrate was almost exclusivelyderived from soil nitrification processes withpotentially minor nitrate contributions fromatmospheric deposition in some catchments. Inwatersheds with significant agricultural andurban land use, concentrations of riverinenitrate were as high as 2.6 mg NO3
–-NL–1 with 15Nnitratevalues between +5 and +8 and18Onitrate values generallybelow +15. Correlations between nitrateconcentrations, 15Nnitratevalues, and N fluxes suggest that nitrate inwaste water constituted a major, and nitrate inmanure a minor additional source of riverinenitrate. Atmospheric nitrate deposition ornitrate-containing fertilizers were not asignificant source of riverine nitrate inwatersheds with significant agricultural andurban land use. Although complementary studiesindicate that in-stream denitrification wassignificant in all rivers, the isotopiccomposition of riverine nitrate sampled at theoutlet of the 16 watersheds did not provideevidence for denitrification in the form ofelevated 15Nnitrate and18Onitrate values. Relativelylow isotopic enrichment factors for nitrogenand oxygen during in-stream denitrification andcontinuous admixture of nitrate from theabove-described sources are thought to beresponsible for this finding. 相似文献
189.
In Vivo Substitution of Choline for Sodium Evokes a Selective Osmoinsensitive Increase of Extracellular Taurine in the Rat Hippocampus 总被引:1,自引:0,他引:1
Recent investigations have demonstrated that taurine and phosphoethanolamine (PEA) are the amino acids most sensitive to microdialysis-perfusion with reduced concentrations of NaCl. The aim of the present work was to assess the importance of Na+ deficiency in evoking this response. Further, the previously described selectivity of replacement of Cl- with acetate with respect to amino acid release was reinvestigated. The hippocampus of urethane-anesthetized rats was dialyzed with Krebs-Ringer bicarbonate buffer, and amino acid concentrations of the perfusate were determined. Choline chloride was then stepwise substituted for NaCl, and, in some cases, mannitol (122 mM) was included in low sodium-containing media. In other experiments, NaCl was replaced with sodium acetate. The dialysate levels of taurine increased selectively in response to Na+ substitution. The elevation of taurine was linearly related to the increase in choline chloride, and maximal levels amounted to 335% of basal levels. The increase in extracellular taurine was not inhibited by perfusion with medium made hyperosmotic with mannitol. Replacement of Cl- with acetate stimulated the release of taurine to 652% of resting levels. In addition, PEA levels increased to 250% of control concentration. Other amino acids were unaffected by Cl- substitution. The results show that taurine transport is considerably more sensitive to Na+ depletion than glutamate transport, which also is known to be Na+ dependent. The taurine increase evoked by low Na+ is not caused by cellular swelling as it was unaffected by hyperosmolar medium. Finally, substitution of acetate for Cl- causes a specific elevation of extracellular taurine and PEA, possibly as a result of cytotoxic edema. 相似文献
190.
Villain M Tournoud C Flesch F Cirimele V Kintz P 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2006,842(2):111-115
Among the drugs that are used to incapacitate victims such as kids or elderly for sedation or for criminal gain such as sexual offences or robberies, glibenclamide, an antidiabetic was never mentioned. To document the interest of hair testing in such forensic situations, we have developed an original method to test for glibenclamide. A 30-year-old man was admitted to the Emergency Unit for coma and seizures after a party with some members of his family. Blood glucose was 0.40 g/l. A hair specimen was collected several weeks after the event and divided into two segments of 2 cm. Twenty milligrams of each segment cut into small pieces were incubated overnight in a phosphate buffer (pH 5.5), in presence of gliclazide used as internal standard (IS). A liquid/liquid extraction was realized with a mixture of diethyl ether/methylene chloride, and hair extract was separated on a XTerra MS C18 column using a gradient of acetonitrile and formate buffer. Detection of glibenclamide was achieved using two transitions: m/z 493.9 to 168.9 and 493.9 to 368.8. Linearity was observed from 5 to 1000 pg/mg (r2 = 0.956) with a limit of quantification at 5 pg/mg and a clean-up recovery of about 61%. Within-batch precision and bias were 9.0 and 9.5%, respectively. Ion suppression tested on drug-free hair was about 50%. Glibenclamide tested positive in the two consecutive segments (root to 2 cm: 23 pg/mg and 2-4 cm: 31 pg/mg). These findings were in accordance with a repetitive exposure to the drug. The concentrations were compared with those obtained after a single and a daily dose administration. In the hair of a subject receiving a single 5mg dose and collected 4 weeks later, glibenclamide was detected in the proximal segment at 5 pg/mg. After a 20 mg/day dose, the hair concentration of a subject under glibenclamide therapy was 650 pg/mg. 相似文献