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121.
Yin-Chieh Lai Chung-Feng Kao Mong-Liang Lu Hsi-Chung Chen Po-Yu Chen Chien-Hsiun Chen Winston W. Shen Jer-Yuarn Wu Ru-Band Lu Po-Hsiu Kuo 《PloS one》2015,10(3)
Several genes that are involved in the regulation of circadian rhythms are implicated in the susceptibility to bipolar disorder (BD). The current study aimed to investigate the relationships between genetic variants in NR1D1 RORA, and RORB genes and BD in the Han Chinese population. We conducted a case-control genetic association study with two samples of BD patients and healthy controls. Sample I consisted of 280 BD patients and 200 controls. Sample II consisted of 448 BD patients and 1770 healthy controls. 27 single nucleotide polymorphisms in the NR1D1, RORA, and RORB genes were genotyped using GoldenGate VeraCode assays in sample I, and 492 markers in the three genes were genotyped using Affymetrix Genome-Wide CHB Array in sample II. Single marker and gene-based association analyses were performed using PLINK. A combined p-value for the joining effects of all markers within a gene was calculated using the rank truncated product method. Multifactor dimensionality reduction (MDR) method was also applied to test gene-gene interactions in sample I. All markers were in Hardy-Weinberg equilibrium (P>0.001). In sample I, the associations with BD were observed for rs4774388 in RORA (OR = 1.53, empirical p-value, P = 0.024), and rs1327836 in RORB (OR = 1.75, P = 0.003). In Sample II, there were 45 SNPs showed associations with BD, and the most significant marker in RORA was rs11639084 (OR = 0.69, P = 0.002), and in RORB was rs17611535 (OR = 3.15, P = 0.027). A combined p-value of 1.6×10−6, 0.7, and 1.0 was obtained for RORA, RORB and NR1D1, respectively, indicting a strong association for RORA with the risk of developing BD. A four way interaction was found among markers in NR1D1, RORA, and RORB with the testing accuracy 53.25% and a cross-validation consistency of 8 out of 10. In sample II, 45 markers had empirical p-values less than 0.05. The most significant markers in RORA and RORB genes were rs11639084 (OR = 0.69, P = 0.002), and rs17611535 (OR = 3.15, P = 0.027), respectively. Gene-based association was significant for RORA gene (P = 0.0007). Our results support for the involvement of RORs genes in the risk of developing BD. Investigation of the functional properties of genes in the circadian pathway may further enhance our understanding about the pathogenesis of bipolar illness. 相似文献
122.
In 2010, foreign-born persons accounted for 60% of all tuberculosis (TB) cases in the United States. Understanding which national groups make up the highest proportion of TB cases will assist TB control programs in concentrating limited resources where they can provide the greatest impact on preventing transmission of TB disease. The objective of our study was to predict through 2020 the numbers of U.S. TB cases among U.S.-born, foreign-born and foreign-born persons from selected countries of birth. TB case counts reported through the National Tuberculosis Surveillance System from 2000–2010 were log-transformed, and linear regression was performed to calculate predicted annual case counts and 95% prediction intervals for 2011–2020. Data were analyzed in 2011 before 2011 case counts were known. Decreases were predicted between 2010 observed and 2020 predicted counts for total TB cases (11,182 to 8,117 [95% prediction interval 7,262–9,073]) as well as TB cases among foreign-born persons from Mexico (1,541 to 1,420 [1,066–1,892]), the Philippines (740 to 724 [569–922]), India (578 to 553 [455–672]), Vietnam (532 to 429 [367–502]) and China (364 to 328 [249–433]). TB cases among persons who are U.S.-born and foreign-born were predicted to decline 47% (4,393 to 2,338 [2,113–2,586]) and 6% (6,720 to 6,343 [5,382–7,476]), respectively. Assuming rates of declines observed from 2000–2010 continue until 2020, a widening gap between the numbers of U.S.-born and foreign-born TB cases was predicted. TB case count predictions will help TB control programs identify needs for cultural competency, such as languages and interpreters needed for translating materials or engaging in appropriate community outreach. 相似文献
123.
Social network characteristics associated with weight loss among black and hispanic adults 下载免费PDF全文
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Jay Vornhagen Christine M. Bassis Srividya Ramakrishnan Robert Hein Sophia Mason Yehudit Bergman Nicole Sunshine Yunfan Fan Caitlyn L. Holmes Winston Timp Michael C. Schatz Vincent B. Young Patricia J. Simner Michael A. Bachman 《PLoS pathogens》2021,17(4)
Klebsiella pneumoniae (Kp) is an important cause of healthcare-associated infections, which increases patient morbidity, mortality, and hospitalization costs. Gut colonization by Kp is consistently associated with subsequent Kp disease, and patients are predominantly infected with their colonizing strain. Our previous comparative genomics study, between disease-causing and asymptomatically colonizing Kp isolates, identified a plasmid-encoded tellurite (TeO3-2)-resistance (ter) operon as strongly associated with infection. However, TeO3-2 is extremely rare and toxic to humans. Thus, we used a multidisciplinary approach to determine the biological link between ter and Kp infection. First, we used a genomic and bioinformatic approach to extensively characterize Kp plasmids encoding the ter locus. These plasmids displayed substantial variation in plasmid incompatibility type and gene content. Moreover, the ter operon was genetically independent of other plasmid-encoded virulence and antibiotic resistance loci, both in our original patient cohort and in a large set (n = 88) of publicly available ter operon-encoding Kp plasmids, indicating that the ter operon is likely playing a direct, but yet undescribed role in Kp disease. Next, we employed multiple mouse models of infection and colonization to show that 1) the ter operon is dispensable during bacteremia, 2) the ter operon enhances fitness in the gut, 3) this phenotype is dependent on the colony of origin of mice, and 4) antibiotic disruption of the gut microbiota eliminates the requirement for ter. Furthermore, using 16S rRNA gene sequencing, we show that the ter operon enhances Kp fitness in the gut in the presence of specific indigenous microbiota, including those predicted to produce short chain fatty acids. Finally, administration of exogenous short-chain fatty acids in our mouse model of colonization was sufficient to reduce fitness of a ter mutant. These findings indicate that the ter operon, strongly associated with human infection, encodes factors that resist stress induced by the indigenous gut microbiota during colonization. This work represents a substantial advancement in our molecular understanding of Kp pathogenesis and gut colonization, directly relevant to Kp disease in healthcare settings. 相似文献
126.
Giles W. Story Ivaylo Vlaev Ben Seymour Joel S. Winston Ara Darzi Raymond J. Dolan 《PLoS computational biology》2013,9(11)
Standard theories of decision-making involving delayed outcomes predict that people should defer a punishment, whilst advancing a reward. In some cases, such as pain, people seem to prefer to expedite punishment, implying that its anticipation carries a cost, often conceptualized as ‘dread’. Despite empirical support for the existence of dread, whether and how it depends on prospective delay is unknown. Furthermore, it is unclear whether dread represents a stable component of value, or is modulated by biases such as framing effects. Here, we examine choices made between different numbers of painful shocks to be delivered faithfully at different time points up to 15 minutes in the future, as well as choices between hypothetical painful dental appointments at time points of up to approximately eight months in the future, to test alternative models for how future pain is disvalued. We show that future pain initially becomes increasingly aversive with increasing delay, but does so at a decreasing rate. This is consistent with a value model in which moment-by-moment dread increases up to the time of expected pain, such that dread becomes equivalent to the discounted expectation of pain. For a minority of individuals pain has maximum negative value at intermediate delay, suggesting that the dread function may itself be prospectively discounted in time. Framing an outcome as relief reduces the overall preference to expedite pain, which can be parameterized by reducing the rate of the dread-discounting function. Our data support an account of disvaluation for primary punishments such as pain, which differs fundamentally from existing models applied to financial punishments, in which dread exerts a powerful but time-dependent influence over choice. 相似文献
127.
Thibault B. Ali Thomas R. Schleret Brian M. Reilly Winston Yuchen Chen Ruben Abagyan 《PloS one》2015,10(12)
This survey analyzes two national pharmacovigilance databases in order to determine the major adverse reactions observed with the use of cholinesterase inhibitors in dementia. We conducted a statistical analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) and the Canada Vigilance Adverse Reaction Database (CVARD) concerning the side effects of cholinesterase inhibitors. The statistics calculated for each adverse event were the frequency and the reporting odds ratios (ROR). A total of 9877 and 2247 reports were extracted from the FAERS and CVARD databases, respectively. A disproportionately higher frequency of reports of death as an adverse event for rivastigmine, compared to the other acetylcholinesterase inhibiting drugs, was observed in both the FAERS (ROR = 3.42; CI95% = 2.94–3.98; P<0.0001) and CVARD (ROR = 3.67; CI95% = 1.92–7.00; P = 0.001) databases. While cholinesterase inhibitors remain to be an important therapeutic tool against Alzheimer’s disease, the disproportionate prevalence of fatal outcomes with rivastigmine compared with alternatives should be taken into consideration. 相似文献
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Gerald C. Llewellyn Peter C. Sherertz Carl W. Armstrong Grayson B. Miller Jr. John D. Reynolds T. Daniel Kimbrough George A. Bean Winston M. Hagler Jr. Carol A. Haney Carol S. Trempus Charles E. O'Rear William V. Dashek 《Journal of industrial microbiology & biotechnology》1988,3(6):351-356
Summary A pre-evaluation of the samples of both buckwheat and rice hulls, planned for use as pillow fill-materials, showed the presence ofAspergillus flavus, A glaucus, andPenicillium spp. Buckwheat- and rice-hull media (BHM and RHM) inoculated withA. flavus both supported the production of aflatoxins (AFB1 and AFG1) in the parts per million (ppm) range; BHM yielded approximately twice the quantity of both AFB1 and AFG1 than did RHM. Both BHM and RHM inoculated withFusarium tricinctum yielded trichothecenes (T-2 toxins) in the ppm range, with the BHM producing approximately three times more T-2 toxins than the RHM. Also,F. tricinctum grown on both media produced several metabolites which included HT-2, 3-OH T-2, neosolariol, T-2 triol, and T-2 tetraol. The BHM yielded all of the above, while the RHM failed to support the production of the 3-OH T-2 toxin. In addition, neither medium inoculated withMyrothecium roridum yielded any detectable levels of macrocyclic trichothecenes. The results indicated that these materials have the potential to become contaminated with mycotoxins. 相似文献
130.