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121.
Stool specimens were examined for the parasite Trichuris trichiura from 1,860 patients in 17 hospitals for the mentally subnormal in the U.K. It was found in 10 of these hospitals, and an overall incidence of 13·2% was recorded. Most cases occurred in the South, where the overall incidence was 36·3%.Difetarsone was used in the treatment of infestations in two hospitals, and proved to be very well tolerated, cure rates of 81 to 88% being obtained. 相似文献
122.
In 18 women with uncomplicated pregnancies smoking two cigarettes significantly reduced the proportion of the time that fetal breathing movements were present. 相似文献
123.
Behavioral and computational studies predict that synaptic plasticity of excitatory mossy fiber inputs to cerebellar nuclear neurons is required for associative learning, but standard tetanization protocols fail to potentiate nuclear cell EPSCs in mouse cerebellar slices. Nuclear neurons fire action potentials spontaneously unless strongly inhibited by Purkinje neurons, raising the possibility that plasticity-triggering signals in these cells differ from those at classical Hebbian synapses. Based on predictions of neuronal activity during delay eyelid conditioning, we developed quasi-physiological induction protocols consisting of high-frequency mossy fiber stimulation and postsynaptic hyperpolarization. Robust, NMDA receptor-dependent potentiation of nuclear cell EPSCs occurred with protocols including a 150-250 ms hyperpolarization in which mossy fiber stimulation preceded a postinhibitory rebound depolarization. Mossy fiber stimulation potentiated EPSCs even when postsynaptic spiking was prevented by voltage-clamp, as long as rebound current was evoked. These data suggest that Purkinje cell inhibition guides the strengthening of excitatory synapses in the cerebellar nuclei. 相似文献
124.
O'Neill PM Verissimo E Ward SA Davies J Korshin EE Araujo N Pugh MD Cristiano ML Stocks PA Bachi MD 《Bioorganic & medicinal chemistry letters》2006,16(11):2991-2995
A Diels-Alder/thiol-olefin co-oxygenation approach to the synthesis of novel bicyclic endoperoxides 17a-22b is reported. Some of these endoperoxides (e.g., 17b, 19b, 22a and 22b) have potent nanomolar in vitro antimalarial activity equivalent to that of the synthetic antimalarial agent arteflene. Iron(II)-mediated degradation of sulfone-endoperoxide 19b and spin-trapping with TEMPO provide a spin-trapped adduct 25 indicative of the formation of a secondary carbon centered radical species 24. Reactive C-radical intermediates of this type may be involved in the expression of the antimalarial effect of these bicyclic endoperoxides. 相似文献
125.
Calvert PD Strissel KJ Schiesser WE Pugh EN Arshavsky VY 《Trends in cell biology》2006,16(11):560-568
The dynamic localization of proteins within cells is often determined by environmental stimuli. In retinal photoreceptors, light exposure results in the massive translocation of three key signal transduction proteins, transducin, arrestin and recoverin, into and out of the outer segment compartment where phototransduction takes place. This phenomenon has rapidly taken the center stage of photoreceptor cell biology, thanks to the introduction of new quantitative and transgenic approaches. Here, we discuss evidence that intracellular protein translocation contributes to adaptation of photoreceptors to diurnal changes in ambient light intensity and summarize the current debate on whether it is driven by diffusion or molecular motors. 相似文献
126.
Background
Development of efficient analytic methodologies for combining microarray results is a major challenge in gene expression analysis. The widely used effect size models are thought to provide an efficient modeling framework for this purpose, where the measures of association for each study and each gene are combined, weighted by the standard errors. A significant disadvantage of this strategy is that the quality of different data sets may be highly variable, but this information is usually neglected during the integration. Moreover, it is widely known that the estimated standard deviations are probably unstable in the commonly used effect size measures (such as standardized mean difference) when sample sizes in each group are small. 相似文献127.
Eric M Mortensen Laurel A Copeland Mary Jo V Pugh Marcos I Restrepo Rosa Malo de Molina Brandy Nakashima Antonio Anzueto 《Respiratory research》2009,10(1):45
Background
The purpose of our study was to examine the association of prior outpatient use of statins and angiotensin converting enzyme (ACE) inhibitors on mortality for subjects ≥ 65 years of age hospitalized with acute COPD exacerbations.Methods
We conducted a retrospective national cohort study using Veterans Affairs administrative data including subjects ≥65 years of age hospitalized with a COPD exacerbation. Our primary analysis was a multilevel model with the dependent variable of 90-day mortality and hospital as a random effect, controlling for preexisting comorbid conditions, demographics, and other medications prescribed.Results
We identified 11,212 subjects with a mean age of 74.0 years, 98% were male, and 12.4% of subjects died within 90-days of hospital presentation. In this cohort, 20.3% of subjects were using statins, 32.0% were using ACE inhibitors or angiotensin II receptor blockers (ARB). After adjusting for potential confounders, current statin use (odds ratio 0.51, 95% confidence interval 0.40–0.64) and ACE inhibitor/ARB use (0.55, 0.46–0.66) were significantly associated with decreased 90-day mortality.Conclusion
Use of statins and ACE inhibitors prior to admission is associated with decreased mortality in subjects hospitalized with a COPD exacerbation. Randomized controlled trials are needed to examine whether the use of these medications are protective for those patients with COPD exacerbations. 相似文献128.
Steven JM Jones Janessa Laskin Yvonne Y Li Obi L Griffith Jianghong An Mikhail Bilenky Yaron S Butterfield Eric Chuah Richard Corbett Anthony Fejes Simon Chan Nancy Liao Katayoon Kasaian Malachi Griffith John Yee Montgomery Martin Michael Mayo Nataliya Melnyk Ryan D Morin Trevor J Pugh Tesa Severson Sohrab P Shah Margaret Sutcliffe Angela Tam Jefferson Terry Nina Thiessen Thomas Thomson Richard Varhol Thomas Zeng Yongjun Zhao Richard A Moore David G Huntsman Inanc Birol Martin Hirst Robert A Holt Marco A Marra 《Genome biology》2010,11(Z1):I5
129.
Steven JM Jones Janessa Laskin Yvonne Y Li Obi L Griffith Jianghong An Mikhail Bilenky Yaron S Butterfield Timothee Cezard Eric Chuah Richard Corbett Anthony P Fejes Malachi Griffith John Yee Montgomery Martin Michael Mayo Nataliya Melnyk Ryan D Morin Trevor J Pugh Tesa Severson Sohrab P Shah Margaret Sutcliffe Angela Tam Jefferson Terry Nina Thiessen Thomas Thomson Richard Varhol Thomas Zeng Yongjun Zhao Richard A Moore David G Huntsman Inanc Birol Martin Hirst Robert A Holt Marco A Marra 《Genome biology》2010,11(8):1-12
Background
Adenocarcinomas of the tongue are rare and represent the minority (20 to 25%) of salivary gland tumors affecting the tongue. We investigated the utility of massively parallel sequencing to characterize an adenocarcinoma of the tongue, before and after treatment.Results
In the pre-treatment tumor we identified 7,629 genes within regions of copy number gain. There were 1,078 genes that exhibited increased expression relative to the blood and unrelated tumors and four genes contained somatic protein-coding mutations. Our analysis suggested the tumor cells were driven by the RET oncogene. Genes whose protein products are targeted by the RET inhibitors sunitinib and sorafenib correlated with being amplified and or highly expressed. Consistent with our observations, administration of sunitinib was associated with stable disease lasting 4 months, after which the lung lesions began to grow. Administration of sorafenib and sulindac provided disease stabilization for an additional 3 months after which the cancer progressed and new lesions appeared. A recurring metastasis possessed 7,288 genes within copy number amplicons, 385 genes exhibiting increased expression relative to other tumors and 9 new somatic protein coding mutations. The observed mutations and amplifications were consistent with therapeutic resistance arising through activation of the MAPK and AKT pathways.Conclusions
We conclude that complete genomic characterization of a rare tumor has the potential to aid in clinical decision making and identifying therapeutic approaches where no established treatment protocols exist. These results also provide direct in vivo genomic evidence for mutational evolution within a tumor under drug selection and potential mechanisms of drug resistance accrual. 相似文献130.
Monkeypox is a zoonotic viral disease that occurs primarily in Central and West Africa. A recent outbreak in the United States heightened public health concerns for susceptible human populations. Vaccinating with vaccinia virus to prevent smallpox is also effective for monkeypox due to a high degree of sequence conservation. Yet, the identity of antigens within the monkeypox virus proteome contributing to immune responses has not been described in detail. We compared antibody responses to monkeypox virus infection and human smallpox vaccination by using a protein microarray covering 92-95% (166-192 proteins) of representative proteomes from monkeypox viral clades of Central and West Africa, including 92% coverage (250 proteins) of the vaccinia virus proteome as a reference orthopox vaccine. All viral gene clones were verified by sequencing and purified recombinant proteins were used to construct the microarray. Serum IgG of cynomolgus macaques that recovered from monkeypox recognized at least 23 separate proteins within the orthopox proteome, while only 14 of these proteins were recognized by IgG from vaccinated humans. There were 12 of 14 antigens detected by sera of human vaccinees that were also recognized by IgG from convalescent macaques. The greatest level of IgG binding for macaques occurred with the structural proteins F13L and A33R, and the membrane scaffold protein D13L. Significant IgM responses directed towards A44R, F13L and A33R of monkeypox virus were detected before onset of clinical symptoms in macaques. Thus, antibodies from vaccination recognized a small number of proteins shared with pathogenic virus strains, while recovery from infection also involved humoral responses to antigens uniquely recognized within the monkeypox virus proteome. 相似文献