全文获取类型
收费全文 | 1840篇 |
免费 | 275篇 |
国内免费 | 7篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 40篇 |
妇产科学 | 46篇 |
基础医学 | 292篇 |
口腔科学 | 35篇 |
临床医学 | 277篇 |
内科学 | 260篇 |
皮肤病学 | 34篇 |
神经病学 | 103篇 |
特种医学 | 84篇 |
外科学 | 280篇 |
综合类 | 43篇 |
一般理论 | 1篇 |
预防医学 | 264篇 |
眼科学 | 9篇 |
药学 | 179篇 |
中国医学 | 1篇 |
肿瘤学 | 171篇 |
出版年
2021年 | 27篇 |
2020年 | 31篇 |
2019年 | 25篇 |
2018年 | 42篇 |
2017年 | 24篇 |
2016年 | 34篇 |
2015年 | 27篇 |
2014年 | 56篇 |
2013年 | 43篇 |
2012年 | 91篇 |
2011年 | 80篇 |
2010年 | 46篇 |
2009年 | 33篇 |
2008年 | 62篇 |
2007年 | 88篇 |
2006年 | 79篇 |
2005年 | 74篇 |
2004年 | 79篇 |
2003年 | 60篇 |
2002年 | 71篇 |
2001年 | 52篇 |
2000年 | 64篇 |
1999年 | 57篇 |
1998年 | 21篇 |
1997年 | 21篇 |
1996年 | 20篇 |
1992年 | 32篇 |
1991年 | 44篇 |
1990年 | 36篇 |
1989年 | 46篇 |
1988年 | 59篇 |
1987年 | 42篇 |
1986年 | 34篇 |
1985年 | 39篇 |
1984年 | 32篇 |
1983年 | 30篇 |
1982年 | 19篇 |
1981年 | 18篇 |
1980年 | 16篇 |
1979年 | 36篇 |
1978年 | 25篇 |
1977年 | 18篇 |
1976年 | 21篇 |
1975年 | 25篇 |
1974年 | 19篇 |
1973年 | 17篇 |
1972年 | 24篇 |
1970年 | 21篇 |
1969年 | 15篇 |
1967年 | 16篇 |
排序方式: 共有2122条查询结果,搜索用时 15 毫秒
51.
52.
Mao K Milne RI Zhang L Peng Y Liu J Thomas P Mill RR Renner SS 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(20):7793-7798
Most extant genus-level radiations in gymnosperms are of Oligocene age or younger, reflecting widespread extinction during climate cooling at the Oligocene/Miocene boundary [~23 million years ago (Ma)]. Recent biogeographic studies have revealed many instances of long-distance dispersal in gymnosperms as well as in angiosperms. Acting together, extinction and long-distance dispersal are likely to erase historical biogeographic signals. Notwithstanding this problem, we show that phylogenetic relationships in the gymnosperm family Cupressaceae (162 species, 32 genera) exhibit patterns expected from the Jurassic/Cretaceous breakup of Pangea. A phylogeny was generated for 122 representatives covering all genera, using up to 10,000 nucleotides of plastid, mitochondrial, and nuclear sequence per species. Relying on 16 fossil calibration points and three molecular dating methods, we show that Cupressaceae originated during the Triassic, when Pangea was intact. Vicariance between the two subfamilies, the Laurasian Cupressoideae and the Gondwanan Callitroideae, occurred around 153 Ma (124-183 Ma), when Gondwana and Laurasia were separating. Three further intercontinental disjunctions involving the Northern and Southern Hemisphere are coincidental with or immediately followed the breakup of Pangea. 相似文献
53.
Nicholas S. Kirkby Martina H. Lundberg Louise S. Harrington Philip D. M. Leadbeater Ginger L. Milne Claire M. F. Potter Malak Al-Yamani Oladipupo Adeyemi Timothy D. Warner Jane A. Mitchell 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(43):17597-17602
Prostacyclin is an antithrombotic hormone produced by the endothelium, whose production is dependent on cyclooxygenase (COX) enzymes of which two isoforms exist. It is widely believed that COX-2 drives prostacyclin production and that this explains the cardiovascular toxicity associated with COX-2 inhibition, yet the evidence for this relies on indirect evidence from urinary metabolites. Here we have used a range of experimental approaches to explore which isoform drives the production of prostacyclin in vitro and in vivo. Our data show unequivocally that under physiological conditions it is COX-1 and not COX-2 that drives prostacyclin production in the cardiovascular system, and that urinary metabolites do not reflect prostacyclin production in the systemic circulation. With the idea that COX-2 in endothelium drives prostacyclin production in healthy individuals removed, we must seek new answers to why COX-2 inhibitors increase the risk of cardiovascular events to move forward with drug discovery and to enable more informed prescribing advice. 相似文献
54.
Saminathan A Vinoth KJ Wescott DC Pinkerton MN Milne TJ Cao T Meikle MC 《Journal of periodontal research》2012,47(2):212-221
Saminathan A, Vinoth KJ, Wescott DC, Pinkerton MN, Milne TJ, Cao T, Meikle MC. The effect of cyclic mechanical strain on the expression of adhesion‐related genes by periodontal ligament cells in two‐dimensional culture. J Periodont Res 2012; 47: 212–221. © 2011 John Wiley & Sons A/S Background and Objective: Cell adhesion plays important roles in maintaining the structural integrity of connective tissues and sensing changes in the biomechanical environment of cells. The objective of the present investigation was to extend our understanding of the effect of cyclic mechanical strain on the expression of adhesion‐related genes by human periodontal ligament cells. Material and Methods: Cultured periodontal ligament cells were subjected to a cyclic in‐plane tensile deformation of 12% for 5 s (0.2 Hz) every 90 s for 6–24 h in a Flexercell FX‐4000 Strain Unit. The following parameters were measured: (i) cell viability by the MTT assay; (ii) caspase‐3 and ‐7 activity; and (iii) the expression of 84 genes encoding adhesion‐related molecules using real‐time RT‐PCR microarrays. Results: Mechanical stress reduced the metabolic activity of deformed cells at 6 h, and caspase‐3 and ‐7 activity at 6 and 12 h. Seventy‐three genes were detected at critical threshold values < 35. Fifteen showed a significant change in relative expression: five cell adhesion molecules (ICAM1, ITGA3, ITGA6, ITGA8 and NCAM1), three collagen α‐chains (COL6A1, COL8A1 and COL11A1), four MMPs (ADAMTS1, MMP8, MMP11 and MMP15), plus CTGF, SPP1 and VTN. Four genes were upregulated (ADAMTS1, CTGF, ICAM1 and SPP1) and 11 downregulated, with the range extending from a 1.76‐fold induction of SPP1 at 12 h to a 2.49‐fold downregulation of COL11A1 at 24 h. Conclusion: The study has identified several mechanoresponsive adhesion‐related genes, and shown that onset of mechanical stress was followed by a transient reduction in overall cellular activity, including the expression of two apoptosis ‘executioner’ caspases. 相似文献
55.
Milne AN Sitarz R Carvalho R Polak MM Ligtenberg M Pauwels P Offerhaus GJ Weterman MA 《Human pathology》2007,38(6):903-913
We report the molecular characterization of 8 primary gastric carcinomas, corresponding xenografts, and 2 novel gastric carcinoma cell lines. We compared the tumors and cell lines, with respect to histology, immunohistochemistry, copy number, and hypermethylation of up to 38 genes using methylation-specific multiplex ligation-dependent probe amplification, and TP53 and CDH1 mutation analysis where relevant. The primary tumors and xenografts were histologically comparable and shared expression of 11 of 14 immunohistochemical markers (E-cadherin, beta-catenin, COX-2, p53, p16, TFF1, cyclin E, MLH1, SMAD4, p27, KLK3, CASR, CHFR, and DAPK1). Gains of CASR, DAPK1, and KLK3--not yet described in gastric cancer--were present in the primary tumors, xenografts, and cell lines. The most prominent losses occurred at CDKN2A (p16), CDKN2B (p15), CDKN1B (p27/KIP1), and ATM. Except for ATM, these losses were found only in the cell line or xenograft, suggesting an association with tumor progression. However, examination of p16 and p27 in 174 gastric cancers using tissue microarrays revealed no significant correlation with tumor stage or lymph node status. Further losses and hypermethylation were detected for MLH1, CHFR, RASSF1, and ESR, and were also seen in primary tumors. Loss of CHFR expression correlated significantly with the diffuse phenotype. Interestingly, we found the highest rate of methylation in primary tumors which gave rise to cell lines. In addition, both cell lines harbored mutations in CDH1, encoding E-cadherin. Xenografts and gastric cancer cell lines remain an invaluable research tool in the uncovering of the multistep progression of cancer. The frequent gains, losses, and hypermethylation reported in this study indicate that the involved genes or chromosomal regions may be relevant to gastric carcinogenesis. 相似文献
56.
Advances in small molecules promoting neurotrophic function 总被引:1,自引:0,他引:1
Nerve growth factor (NGF) and other members of the neurotrophin family are critical for the survival and differentiation of neurons and have been implicated in the pathophysiology of numerous disease states. Although the therapeutic potential of neurotrophins has generated much excitement over the past decade, inconvenient pharmacokinetics and adverse side-effect profiles have limited the clinical usefulness of neurotrophic factors themselves. Compounds that mimic neurotrophin signaling and overcome the pharmacokinetic and side-effect barriers may have greater therapeutic potential. Here, we review the progress to date of clinical trials with direct neurotrophin modulators and describe alternative strategies to target (modulate) neurotrophin production and/or their signal transduction pathways. Particular emphasis is placed on small molecules that are able to modulate neurotrophin function in diseases of the nervous system. These alternative strategies show promise in preclinical studies, with some advancing into clinical development. Moreover, the recognition that clinically effective therapeutics, such as antidepressants and immunophilin ligands, can modulate neurotrophin function suggests that the concept of small molecule therapeutics that promote neurotrophic function may still be viable. 相似文献
57.
58.
Ailsa J. Oswald Jackie Berg Garry Milne Stuart H. Ralston 《Calcified tissue international》2014,94(2):176-182
Teriparatide (TPTD) is often used for the treatment of patients with severe osteoporosis, but its effectiveness in this patient group has not been specifically studied. Here, we report upon the results of an observational study involving 323 patients with severe osteoporosis (bone density T-score of ?4 or less) who were treated at a specialist osteoporosis clinic with TPTD (n = 217) or standard care (n = 106) over a 5.5-year period. The standard care group did not receive TPTD because they declined to self-inject (59.4 %), had a contraindication (7.5 %), or were already stabilized on oral bisphosphonates (33 %). The two groups were matched for the severity of osteoporosis, fracture risk, and most other clinical variables. The annual percentage change in lumbar spine bone mineral density (BMD) was greater in the TPTD group (8.2 ± 6.0 vs. 5.0 ± 8.4, p = 0.002), but there was no difference in response of hip BMD. During follow-up, 3/217 (1.38 %) TPTD-treated patients had new vertebral fractures compared with 7/106 (6.6 %) receiving standard care (p = 0.011), but there was no difference between the groups in the rate of nonvertebral fractures (11.1 vs. 8.5 %, p = 0.47). Logistic regression analysis adjusting for baseline characteristics showed that the risk of vertebral fractures in TPTD-treated patients was significantly reduced compared with standard care (odds ratio = 0.12, 95 % confidence interval 0.03–0.55, p = 0.007). Treatment of severe spinal osteoporosis with TPTD substantially reduces the risk of vertebral fractures compared with standard care and may be the preferred treatment in this patient group. 相似文献
59.
Corey Heitz Justin Morgenstern Christopher Bond William K. Milne 《Academic emergency medicine》2019,26(2):246-249
This is a validation of a preplanned secondary analysis of the NEXUS II Head computed tomography (CT) decision instrument, focusing on the pediatric population. A total of 1,018 patients less than 18 years old, who underwent head CT imaging for blunt head trauma, were included. The decision instrument correctly identified all patient (27/27) who required neurosurgical intervention and 48 of 49 patients who had clinically significant head injury on CT imaging. 相似文献
60.
Christopher Bond Justin Morgenstern Corey Heitz William K. Milne 《Academic emergency medicine》2019,26(4):447-450
Adverse drug events (ADEs) are a significant cause of emergency department (ED) visits in North America and are frequently misdiagnosed. Despite evidence supporting improved health care outcomes for ED patients who have a pharmacist‐led medication review, EDs do not have sufficient clinical pharmacists to perform medication reviews on all patients. The study reviewed in this article aimed to validate clinical decision rules for use by clinical pharmacists and physicians to prioritize ED patients with ADEs. 相似文献