全文获取类型
收费全文 | 479篇 |
免费 | 18篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 18篇 |
儿科学 | 3篇 |
妇产科学 | 6篇 |
基础医学 | 104篇 |
口腔科学 | 4篇 |
临床医学 | 54篇 |
内科学 | 83篇 |
皮肤病学 | 14篇 |
神经病学 | 35篇 |
特种医学 | 12篇 |
外科学 | 26篇 |
综合类 | 3篇 |
一般理论 | 9篇 |
预防医学 | 59篇 |
眼科学 | 4篇 |
药学 | 50篇 |
肿瘤学 | 14篇 |
出版年
2022年 | 3篇 |
2021年 | 9篇 |
2020年 | 3篇 |
2019年 | 6篇 |
2018年 | 10篇 |
2017年 | 9篇 |
2016年 | 7篇 |
2015年 | 20篇 |
2014年 | 18篇 |
2013年 | 23篇 |
2012年 | 21篇 |
2011年 | 31篇 |
2010年 | 16篇 |
2009年 | 22篇 |
2008年 | 39篇 |
2007年 | 29篇 |
2006年 | 17篇 |
2005年 | 9篇 |
2004年 | 23篇 |
2003年 | 16篇 |
2002年 | 12篇 |
2001年 | 13篇 |
2000年 | 7篇 |
1998年 | 3篇 |
1991年 | 2篇 |
1990年 | 6篇 |
1989年 | 6篇 |
1988年 | 12篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 4篇 |
1984年 | 7篇 |
1983年 | 5篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 4篇 |
1977年 | 2篇 |
1974年 | 5篇 |
1968年 | 4篇 |
1966年 | 5篇 |
1965年 | 4篇 |
1961年 | 3篇 |
1960年 | 3篇 |
1959年 | 5篇 |
1957年 | 4篇 |
1955年 | 4篇 |
1954年 | 6篇 |
1949年 | 2篇 |
1932年 | 2篇 |
1929年 | 2篇 |
排序方式: 共有498条查询结果,搜索用时 15 毫秒
31.
Ma W Vincent AL Gramer MR Brockwell CB Lager KM Janke BH Gauger PC Patnayak DP Webby RJ Richt JA 《Proceedings of the National Academy of Sciences of the United States of America》2007,104(52):20949-20954
Although viruses of each of the 16 influenza A HA subtypes are potential human pathogens, only viruses of the H1, H2, and H3 subtype are known to have been successfully established in humans. H2 influenza viruses have been absent from human circulation since 1968, and as such they pose a substantial human pandemic risk. In this report, we isolate and characterize genetically similar avian/swine virus reassortant H2N3 influenza A viruses isolated from diseased swine from two farms in the United States. These viruses contained leucine at position 226 of the H2 protein, which has been associated with increased binding affinity to the mammalian α2,6Gal-linked sialic acid virus receptor. Correspondingly, the H2N3 viruses were able to cause disease in experimentally infected swine and mice without prior adaptation. In addition, the swine H2N3 virus was infectious and highly transmissible in swine and ferrets. Taken together, these findings suggest that the H2N3 virus has undergone some adaptation to the mammalian host and that their spread should be very closely monitored. 相似文献
32.
33.
34.
35.
The recent finding that ribavirin has a mutagenic capacity in a poliovirus replicon model pushing the virus into error catastrophe, provides a possible explanation for the remarkable synergistic effect of ribavirin when combined with interferon in the treatment of chronic hepatitis C virus (HCV)-infected patients. However, ribavirin-induced hypermutation resulting in loss of vital genetic information and viral clearance, does not occur during treatment of HCV-infected patients, as can be inferred from the lack of viral inhibition when treating HCV-infected patients with ribavirin alone. We therefore hypothesized that ribavirin induces mutations in the C-terminal part of the viral NS5A gene, a region found to be correlated with interferon sensitivity. Ribavirin-induced mutations resulting in the appearance of viral variants more sensitive to interferon would explain the synergistic effect of ribavirin when combined with interferon. To test this hypothesis we retrospectively analysed sequences of the C-terminal half of the NS5A gene before and during treatment in six HCV genotype 1-infected patients who had been treated with combination therapy after initial failure to respond permanently to interferon alone. Our results show that during the early treatment phase mutation rate is not enhanced during combination therapy and that, at least in the major variant, shifts in the NS5A domain resulting in the occurrence of viral variants, which are more interferon-sensitive, do not occur. 相似文献
36.
Since the secretory pathway is essential for Candida albicans to transition from a commensal organism to a pathogen, an understanding of how this pathway functions may be beneficial for
identifying novel drug targets to prevent candidiasis. We have cloned the C. albicans KAR2 gene, which performs many roles during the translocation of proteins into the endoplasmic reticulum (ER) during the first
committed step of the secretory pathway in many eukaryotes. Our results show that C. albicans KAR2 is essential, and that the encoded protein rescues a temperature-sensitive growth defect found in a Saccharomyces cerevisiae strain harboring a mutant form of the Kar2 protein. Additionally, S. cerevisiae containing CaKAR2 as the sole copy of this essential gene are viable, and ER microsomes prepared from this strain exhibit wild-type levels
of post-translational translocation during in vitro translocation assays. Finally, ER microsomes isolated from a C. albicans strain expressing reduced amounts of KAR2 mRNA are defective for in vitro translocation of a secreted substrate protein, establishing a new method to study ER translocation
in this organism. Together, these results suggest that C. albicans Kar2p functions during the translocation of proteins into the ER during the first step of the secretory pathway. 相似文献
37.
da Costa Goncalves AC Fontes MA Klussmann E Qadri F Janke J Gollasch M Schleifenbaum J Müller D Jordan J Tank J Luft FC Gross V 《Journal of molecular medicine (Berlin, Germany)》2011,89(12):1219-1229
Central angiotensin II (AngII) plays an important role in the regulation of the sympathetic nervous system. The underlining molecular mechanisms are largely unknown. Spinophilin (SPL) is a regulator of G protein-coupled receptor signaling. Deletion of SPL induces sympathetically mediated arterial hypertension in mice. We tested the hypothesis that SPL restrains blood pressure (BP) by regulating AngII activity. We equipped SPL(-/-) and SPL(+/+) mice with telemetric devices and applied AngII (1.0?mg?kg(-1)?day(-1), minipumps) or the AngII subtype 1 receptor (AT1-R) blocker valsartan (50?mg?kg(-1)?day(-1), gavage). We assessed autonomic nervous system activity through intraperitoneal application of trimethaphan, metoprolol, and atropine. We also tested the effect of intracerebroventricular (icv) AngII on blood pressure in SPL(-/-) and in SPL(+/+) mice. Chronic infusion of AngII upregulates SPL expression in the hypothalamus of SPL(+/+) mice. Compared with SPL(+/+) mice, SPL(-/-) mice showed a greater increase in daytime BP with AngII (19.2?±?0.8 vs. 13.5?±?1.6?mmHg, p?0.05). SPL(-/-) showed a greater depressor response to valsartan. BP and heart rate decreased more with trimethaphan and metoprolol in AngII-treated SPL(-/-) than in AngII-treated SPL(+/+) mice. SPL(-/-) mice responded more to icv AngII. Furthermore, brainstem AT1-R and AngII type 2 receptor (AT2-R) expression was reduced in SPL(-/-) mice. AngII treatment normalized AT1-R and AT2-R expression levels. In summary, our findings suggest that SPL restrains AngII-mediated sympathetic nervous system activation. SPL is a hitherto unrecognized molecule with regard to central blood pressure control and may pave the way to novel strategies for the treatment of hypertension. 相似文献
38.
Amy L. Vincent Wenjun Ma Kelly M. Lager Marie R. Gramer Juergen A. Richt Bruce H. Janke 《Virus genes》2009,39(2):176-185
H1 influenza A viruses that were distinct from the classical swine H1 lineage were identified in pigs in Canada in 2003–2004;
antigenic and genetic characterization identified the hemagglutinin (HA) as human H1 lineage. The viruses identified in Canadian
pigs were human lineage in entirety or double (human–swine) reassortants. Here, we report the whole genome sequence analysis
of four human-like H1 viruses isolated from U.S. swine in 2005 and 2007. All four isolates were characterized as triple reassortants
with an internal gene constellation similar to contemporary U.S. swine influenza virus (SIV), with HA and neuraminidase (NA)
most similar to human influenza virus lineages. A 2007 human-like H1N1 was evaluated in a pathogenesis and transmission model
and compared to a 2004 reassortant H1N1 SIV isolate with swine lineage HA and NA. The 2007 isolate induced disease typical
of influenza virus and was transmitted to contact pigs; however, the kinetics and magnitude differed from the 2004 H1N1 SIV.
This study indicates that the human-like H1 SIV can efficiently replicate and transmit in the swine host and now co-circulates
with contemporary SIVs as a distinct genetic cluster of H1 SIV. 相似文献
39.
40.
Remmerbach TW Maurer K Janke S Schellenberger W Eschrich K Bertolini J Hofmann H Rupf S 《Oral oncology》2011,47(4):278-281
Oral squamous cell carcinomas (OSCCs) often present as advanced tumours requiring aggressive local and regional therapy and result in significant functional impairment. The objective is to develop pre-symptomatic screening detection of OSCC by a brush biopsy method which is less invasive than the conventional biopsy for histology. Given the molecular heterogeneity of oral cancer, it is unlikely that even a panel of tumour markers would provide accurate diagnosis. Therefore, approaches such as the matrix-assisted-laser-desorption/ionisation-time-of-flight-mass-spectrometry (MALDI-TOF-MS) allow several biomarkers or peptide profile patterns to be simultaneously assessed. Brush biopsies from 27 patients with histology-proven OSCCs plus 40 biopsies from 10 healthy controls were collected. MALDI-TOF-MS profiling was performed and additional statistical analysis of the data was used to classify the disease status according to the biological behaviour of the lesion. For classification a support vector machine algorithm was trained using spectra of brush biopsy samples to distinguish healthy control patients from patients with histology-proven OSCC. MALDI-TOF-MS was able to distinguish between healthy patients and OSCC patients with a sensitivity of 100% and specificity of 93%. In summary, MALDI-TOF-MS in combination with sophisticated bioinformatic methods can distinguish OSCC patients from non-cancer controls with excellent sensitivity and specificity. Further improvement and validation of this approach is necessary to determine its feasibility to assist the pre-symptomatic detection of head and neck cancer screening in routine daily practice. 相似文献