全文获取类型
收费全文 | 2266篇 |
免费 | 188篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 15篇 |
儿科学 | 112篇 |
妇产科学 | 30篇 |
基础医学 | 298篇 |
口腔科学 | 78篇 |
临床医学 | 246篇 |
内科学 | 376篇 |
皮肤病学 | 17篇 |
神经病学 | 257篇 |
特种医学 | 31篇 |
外国民族医学 | 1篇 |
外科学 | 449篇 |
综合类 | 50篇 |
一般理论 | 1篇 |
预防医学 | 177篇 |
眼科学 | 17篇 |
药学 | 124篇 |
肿瘤学 | 177篇 |
出版年
2022年 | 19篇 |
2021年 | 30篇 |
2020年 | 21篇 |
2019年 | 53篇 |
2018年 | 47篇 |
2017年 | 25篇 |
2016年 | 43篇 |
2015年 | 42篇 |
2014年 | 45篇 |
2013年 | 80篇 |
2012年 | 96篇 |
2011年 | 107篇 |
2010年 | 76篇 |
2009年 | 51篇 |
2008年 | 120篇 |
2007年 | 121篇 |
2006年 | 90篇 |
2005年 | 93篇 |
2004年 | 95篇 |
2003年 | 76篇 |
2002年 | 80篇 |
2001年 | 88篇 |
2000年 | 72篇 |
1999年 | 64篇 |
1998年 | 15篇 |
1997年 | 16篇 |
1996年 | 17篇 |
1995年 | 15篇 |
1992年 | 46篇 |
1991年 | 47篇 |
1990年 | 30篇 |
1989年 | 36篇 |
1988年 | 31篇 |
1987年 | 26篇 |
1986年 | 35篇 |
1985年 | 44篇 |
1984年 | 34篇 |
1983年 | 26篇 |
1982年 | 23篇 |
1979年 | 19篇 |
1978年 | 17篇 |
1977年 | 15篇 |
1976年 | 19篇 |
1975年 | 24篇 |
1974年 | 29篇 |
1973年 | 21篇 |
1972年 | 18篇 |
1970年 | 18篇 |
1967年 | 17篇 |
1966年 | 14篇 |
排序方式: 共有2456条查询结果,搜索用时 15 毫秒
61.
Deubiquitinating enzyme CYLD negatively regulates the ubiquitin-dependent kinase Tak1 and prevents abnormal T cell responses 总被引:3,自引:0,他引:3
Reiley WW Jin W Lee AJ Wright A Wu X Tewalt EF Leonard TO Norbury CC Fitzpatrick L Zhang M Sun SC 《The Journal of experimental medicine》2007,204(6):1475-1485
The deubiquitinating enzyme CYLD has recently been implicated in the regulation of signal transduction, but its physiological function and mechanism of action are still elusive. In this study, we show that CYLD plays a pivotal role in regulating T cell activation and homeostasis. T cells derived from Cyld knockout mice display a hyperresponsive phenotype and mediate the spontaneous development of intestinal inflammation. Interestingly, CYLD targets a ubiquitin-dependent kinase, transforming growth factor-beta-activated kinase 1 (Tak1), and inhibits its ubiquitination and autoactivation. Cyld-deficient T cells exhibit constitutively active Tak1 and its downstream kinases c-Jun N-terminal kinase and IkappaB kinase beta. These results emphasize a critical role for CYLD in preventing spontaneous activation of the Tak1 axis of T cell signaling and, thereby, maintaining normal T cell function. 相似文献
62.
Responses of terrestrial insects to hypoxia or hyperoxia 总被引:1,自引:0,他引:1
Harrison J Frazier MR Henry JR Kaiser A Klok CJ Rascón B 《Respiratory physiology & neurobiology》2006,154(1-2):4-17
Oxygen is critically important for catabolic ATP generation but is also a dangerous source of reactive oxygen species. Insects respond to short-term exposure to hypoxia or hyperoxia with compensatory changes in spiracular opening and ventilation that reduce variation in internal Po2. Below critical Po2 values (Pc), nitric oxide and hypoxia inducible factor (HIF)-mediated pathways induce long-term responses such as compensatory tracheal growth, suppressed development, and acclimation of ventilation. Pc values are strongly affected by activity and ontogeny, due to changes in the ratio of tracheal conductance to metabolic rate. Although growth rates and development are suppressed by significant hypoxia in all species studied to date, adult body size is only affected in some species. Severe hyperoxia causes major oxidative stress and reduces survival, while moderate hyperoxia increases development times and body sizes in some species by unknown mechanisms. 相似文献
63.
Although the dentate gyrus is one of the primary targets of septo-hippocampal cholinergic afferents, relatively little is known about the cholinergic physiology of neurons in the area. By combining whole cell patch-clamp recording with brief local application of exogenous agonists in horizontal slices, we found that there is robust expression of functional somatic alpha 7-containing nicotinic acetylcholine receptors (nAChRs) on molecular layer interneurons, hilar interneurons, and the glutamatergic mossy cells of the dentate hilus. In contrast, the principal neurons of the dentate gyrus, the granule cells, are generally unresponsive to focal somatic or dendritic application of ACh in the presence of atropine. We also demonstrate that cholinergic activation of alpha 7-containing nAChRs on the subgranular interneurons of the hilus can produce methyllycaconitine-sensitive GABAergic inhibitory postsynaptic currents (IPSCs) in nearby granule cells and enhance the amplitude of an electrically evoked monosynaptic IPSC. Further, activation of alpha 7-containing nAChRs on subgranular interneurons that is timed to coincide with synaptic release of glutamate onto these cells will enhance the functional inhibition of granule cells. These findings suggest that a complex interplay between glutamatergic afferents from the entorhinal cortex and cholinergic afferents from the medial septum could be involved in the normal regulation of granule cell function. Such a relationship between these two afferent pathways could be highly relevant to the study of both age-related memory dysfunction and disorders involving regulation of excitability, such as temporal lobe epilepsy. 相似文献
64.
Judith A Hobert Rebecca Embacher Jessica L Mester Thomas W Frazier II Charis Eng 《European journal of human genetics : EJHG》2014,22(2):273-276
Unlike some other childhood neurodevelopmental disorders, no diagnostic biochemical marker has been identified in all individuals with an autism spectrum disorder (ASD). This deficit likely results from genetic heterogeneity among the population. Therefore, we evaluated a subset of individuals with ASDs, specifically, individuals with or without macrocephaly in the presence or absence of PTEN mutations. We sought to determine if amino or organic acid markers could be used to identify individuals with ASDs with or without macrocephaly in the presence or absence of PTEN mutations, and to establish the degree of macrocephaly in individuals with ASDs and PTEN mutation. Urine, blood and occipital–frontal circumference (OFC) measurements were collected from 69 individuals meeting DSM-IV-TR criteria. Urine and plasma samples were subjected to amino and organic acid analyses. PTEN was Sanger-sequenced from germline genomic DNA. Germline PTEN mutations were identified in 27% (6/22) of the macrocephalic ASD population. All six PTEN mutation-positive individuals were macrocephalic with average OFC+4.35 standard deviations (SDs) above the mean. No common biochemical abnormalities were identified in macrocephalic ASD individuals with or without PTEN mutations. In contrast, among the collective ASD population, elevation of urine aspartic acid (87% 54/62), plasma taurine (69% 46/67) and reduction of plasma cystine (72% 46/64) were observed. PTEN sequencing should be carried out for all individuals with ASDs and macrocephaly with OFC ≥2SDs above the mean. A proportion of individuals with ASDs may have an underlying disorder in sulfur amino acid metabolism. 相似文献
65.
Jessica A Kahn Graham Colditz Gideon N Aweh A Lindsay Frazier 《Ambulatory Pediatrics》2002,2(3):212-217
OBJECTIVES: The pelvic examination is an important component of reproductive health services for adolescent girls and is recommended for those who become sexually active. The aims of this study were to describe self-reported rates of pelvic examinations in sexually active adolescent girls and to determine factors associated with having obtained an examination. METHODS: Cross-sectional data from a national self-administered survey of nurses' adolescent daughters were used. Subjects were those girls (N = 635) who reported ever having had sexual intercourse. Bivariate and multivariate analyses were used to identify demographic and psychological variables, preventive health behaviors, and risk behaviors associated with having ever obtained a pelvic examination. RESULTS: Median subject age was 16.0 years (range 12-19 years), and 46% of subjects reported having had a pelvic examination. Variables associated with having obtained an examination were older age (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.09-1.53), cigarette smoking (OR 1.51, 95% CI 1.02-2.24), higher number of sexual partners (OR 1.29, 95% CI 1.14-1.47), and no condom use during last sexual intercourse (OR 1.80, 95% CI 1.19-2.70). CONCLUSIONS: Fewer than half of these sexually active adolescents had ever obtained a pelvic examination. Younger subjects who did not smoke regularly, had fewer partners, and used condoms were less likely to have obtained an examination; these adolescents may not be seeking reproductive health care services or be recognized by parents or providers as being in need of services. 相似文献
66.
67.
Christopher C. Norbury Benedict J. Chambers Alan R. Prescott Hans-Gustaf Ljunggren Colin Watts 《European journal of immunology》1997,27(1):280-288
Dendritic cells expanded from mouse bone marrow (BMDC) with granulocyte/macrophage-colony-stimulating factor have potent T cell-stimulatory properties both in vitro and in vivo. This has been well documented for major histocompatibility complex (MHC) class II-restricted responses, and more recently using peptide-loaded and protein-pulsed DC for CD8 responses following adoptive transfer in mice. An unresolved question concerns the capacity of BMDC to present exogenous antigen on MHC class I molecules, an unconventional mode of MHC class I loading for which there is now considerable evidence, particularly in macrophages. Here, we show that BMDC exhibit high levels of macropinocytosis driven by constitutive membrane ruffling activity. Up to one-third of actively ruffling and macropinocytosing BMDC transferred pinocytosed horseradish peroxidase into the cytosol following a 15-min pulse, suggesting that they might be capable of presenting exogenous soluble antigen on MHC class I molecules. We show that BMDC presented exogenous ovalbumin to a T cell hybridoma more effectively, more rapidly, and at lower exogenous antigen concentrations than BM macrophages on a cell-for-cell basis. Presentation was TAP dependent, brefeldin A sensitive, and blocked by inhibitors of proteasomal processing, demonstrating use of the classical MHC class I pathway. Although effective presentation of exogenous antigen by BMDC occurred in the absence of agents which stimulate macropinocytosis, treatment with phorbol myristate acetate (PMA) enhanced both pinocytosis and MHC class I presentation by BMDC. Finally, PMA-stimulated BMDC exposed to exogenous ovalbumin in vitro were able to prime an antigen-specific cytotoxic T lymphocyte response following adoptive transfer in vivo. 相似文献
68.
Leroy Frazier LaVonne Ortega Nimeshkumar Patel Jamar Barnes Alex E. Crosby Katherine Hempstead 《Journal of the National Medical Association》2017,109(4):272-278
Background
The National Violent Death Reporting System (NVDRS) captures homicides that law enforcement or coroner/medical examiners deem as gang-related but the criteria used may vary across locations. Also, the existing gang-related variable likely underestimates the number of homicides that are associated with gang activity. This study utilizes NVDRS data to identify “gang-like” homicides which are not currently captured as “gang-related.”Methods
A set of criteria recommended by a panel of experts in gang violence, was applied to homicides collected in the NVDRS. These criteria, termed “gang-like” characteristics, were developed in order to better identify homicides consistent with gang activity. The narratives of the identified cases were then reviewed to refine the operational standard. After the reviews were complete, the typology was modified to finalize the operationalization of “gang-like” homicides.Results
A total of 481 gang-like homicides were identified using the “gang-like” criteria. This represents an increase of almost 69% over the 696 gang-related homicides captured in NVDRS dataset.Gang-like and gang-related homicides combined represented 6.6% of homicides that occurred from 2005 to 2008. Among the 16 states included in this analysis, Colorado (15.5%) and Oklahoma (14%) had the highest percentage of homicides that were either gang-related or gang-like.Maryland had the greatest relative increase (227.3%) between gang related and gang-like homicides.Conclusion
The new “gang-like” variable complements the existing “gang-related” variable by providing an automated, standardized way to identify homicides that have circumstances consistent with gang activity. This new variable might be useful to states and localities seeking an efficient way to monitor homicides potentially resulting from gang activity. Additional efforts are needed to standardize the reporting of homicides associated with gang activity. 相似文献69.
Phenotypic and genetic characterization of clinical isolates of CDC coryneform group A-3: proposal of a new species of Cellulomonas, Cellulomonas denverensis sp. nov 下载免费PDF全文
Brown JM Frazier RP Morey RE Steigerwalt AG Pellegrini GJ Daneshvar MI Hollis DG McNeil MM 《Journal of clinical microbiology》2005,43(4):1732-1737
CDC coryneform group A-3 bacteria are rare human pathogens. In this study, six group A-3 isolates (two from blood, one from cerebrospinal fluid, and one each from homograft valve, lip wound, and pilonidal cyst) were compared to the type strains of phenotypically related organisms, Cellulomonas fimi, Cellulomonas hominis, Oerskovia turbata, and Sanguibacter suarezii, and characterized by phenotypic, chemotaxonomic, and genotypic studies. DNA-DNA reassociation analysis identified two genomic groups, and phylogenetic analysis of the 16S rRNA gene sequence identified the taxonomic positions of these groups to genus level. Two groups were defined, and both were more closely related to Cellulomonas species: one group of three strains, for which we propose the new species Cellulomonas denverensis sp. nov., with the type strain W6929 (ATCC BAA-788(T) or DSM 15764(T)), was related to C. hominis ATCC 51964(T) (98.5% 16S rRNA gene sequence similarity), and the second group of three strains was related to C. hominis ATCC 51964(T) (99.8 to 99.9% 16S rRNA gene sequence similarity). The definition of this new Cellulomonas species and the confirmation of three strains as C. hominis serve to further clarify the complex taxonomy of CDC coryneform group A-3 bacteria and will assist in our understanding of the epidemiology and clinical significance of these microorganisms. 相似文献
70.
M Hill K Finning P Martin J Hogg C Meaney G Norbury G Daniels LS Chitty 《Clinical genetics》2011,80(1):68-75
Hill M, Finning K, Martin P, Hogg J, Meaney C, Norbury G, Daniels G, Chitty LS. Non‐invasive prenatal determination of fetal sex: translating research into clinical practice. The effectiveness and clinical utility of non‐invasive prenatal diagnosis (NIPD) for fetal sex determination using cell‐free fetal DNA (cffDNA) was assessed by undertaking a prospective national audit of UK testing. NIPD was performed using real‐time polymerase chain reaction analysis of the DYS14 or SRY gene in cffDNA extracted from maternal plasma. All cases referred for fetal sex determination from 1 April 2006 to 31 March 2009 were ascertained from two laboratories offering the test. Fetal gender determined by NIPD was compared with that based on ultrasound, invasive test or phenotype at birth. Indication and rate of invasive testing was ascertained. In the first year, results were issued in 150/161 pregnancies tested. Of the 135 with outcome data, results were concordant in 130/135 [96.3% (95% CI 91.6–98.8%)]. Reporting criteria were changed and in the subsequent 511 pregnancies the concordancy rate increased to 401/403 [99.5% (95% CI 98.2–99.9%)]. Over the 3 years only 32.9% (174/528) underwent invasive testing. NIPD for fetal sex determination using cffDNA is highly accurate when performed in National Health Service laboratories if stringent reporting criteria are applied. Parents should be advised of the small risk of discordant results and possible need for repeat testing to resolve inconclusive results. 相似文献