全文获取类型
收费全文 | 2798篇 |
免费 | 151篇 |
国内免费 | 3篇 |
专业分类
耳鼻咽喉 | 44篇 |
儿科学 | 110篇 |
妇产科学 | 46篇 |
基础医学 | 310篇 |
口腔科学 | 45篇 |
临床医学 | 160篇 |
内科学 | 465篇 |
皮肤病学 | 39篇 |
神经病学 | 213篇 |
特种医学 | 105篇 |
外科学 | 342篇 |
综合类 | 80篇 |
预防医学 | 192篇 |
眼科学 | 239篇 |
药学 | 333篇 |
中国医学 | 11篇 |
肿瘤学 | 218篇 |
出版年
2023年 | 15篇 |
2022年 | 49篇 |
2021年 | 63篇 |
2020年 | 27篇 |
2019年 | 50篇 |
2018年 | 54篇 |
2017年 | 39篇 |
2016年 | 56篇 |
2015年 | 57篇 |
2014年 | 74篇 |
2013年 | 106篇 |
2012年 | 194篇 |
2011年 | 184篇 |
2010年 | 92篇 |
2009年 | 86篇 |
2008年 | 118篇 |
2007年 | 138篇 |
2006年 | 125篇 |
2005年 | 117篇 |
2004年 | 115篇 |
2003年 | 98篇 |
2002年 | 87篇 |
2001年 | 63篇 |
2000年 | 72篇 |
1999年 | 79篇 |
1998年 | 31篇 |
1997年 | 18篇 |
1996年 | 21篇 |
1995年 | 17篇 |
1994年 | 14篇 |
1993年 | 17篇 |
1992年 | 66篇 |
1991年 | 56篇 |
1990年 | 55篇 |
1989年 | 51篇 |
1988年 | 27篇 |
1987年 | 37篇 |
1986年 | 36篇 |
1985年 | 32篇 |
1984年 | 31篇 |
1983年 | 30篇 |
1981年 | 14篇 |
1980年 | 17篇 |
1979年 | 22篇 |
1978年 | 19篇 |
1976年 | 14篇 |
1974年 | 17篇 |
1973年 | 35篇 |
1971年 | 15篇 |
1970年 | 18篇 |
排序方式: 共有2952条查询结果,搜索用时 15 毫秒
971.
Tan J Yang X Zhuang L Jiang X Chen W Lee PL Karuturi RK Tan PB Liu ET Yu Q 《Genes & development》2007,21(9):1050-1063
Polycomb-repressive complex 2 (PRC2)-mediated histone methylation plays an important role in aberrant cancer gene silencing and is a potential target for cancer therapy. Here we show that S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A (DZNep) induces efficient apoptotic cell death in cancer cells but not in normal cells. We found that DZNep effectively depleted cellular levels of PRC2 components EZH2, SUZ12, and EED and inhibited associated histone H3 Lys 27 methylation (but not H3 Lys 9 methylation). By integrating RNA interference (RNAi), genome-wide expression analysis, and chromatin immunoprecipitation (ChIP) studies, we have identified a prominent set of genes selectively repressed by PRC2 in breast cancer that can be reactivated by DZNep. We further demonstrate that the preferential reactivation of a set of these genes by DZNep, including a novel apoptosis affector, FBXO32, contributes to DZNep-induced apoptosis in breast cancer cells. Our results demonstrate the unique feature of DZNep as a novel chromatin remodeling compound and suggest that pharmacologic reversal of PRC2-mediated gene repression by DZNep may constitute a novel approach for cancer therapy. 相似文献
972.
T. Telkhade V. Murthy T.S. Kanala J.M. Mathew R. Phurailatpam S. Mokal D. Chourasiya G. Panigrahi R. Krishnatry 《Clinical oncology (Royal College of Radiologists (Great Britain))》2021,33(3):172-180
AimsThe safety and efficacy of stereotactic body radiotherapy (SBRT) in localised prostate cancer are now established through phase III randomised trials. Its utility in node-positive prostate cancer is restricted due to a lack of controlled studies specifically addressing this subgroup. Herein we report the safety and efficacy of SBRT in this subgroup.Materials and methodsIn total, 60 patients treated with SBRT to prostate and pelvis were analysed. All patients received neoadjuvant androgen deprivation therapy for at least 6 months and long-term adjuvant hormonal therapy (70% medical and 30% surgical). All patients were treated with daily image-guided rotational intensity-modulated radiotherapy. The dose delivered to the prostate and gross node was 35–37.5 Gy and 25 Gy in five fractions to the elective pelvic nodal region on alternate days. Acute and late toxicities were graded as per Radiation Therapy Oncology Group common toxicity criteria.ResultsForty-one (68%) patients had a Gleason score ≥8. The median prostate-specific antigen level at diagnosis was 39 ng/ml. Twenty (33%) patients had common iliac nodal uptake on initial prostate-specific membrane antigen positron emission tomography-computed tomography. After the median follow-up of 30 months, no acute or late Radiation Therapy Oncology Group grade ≥3 gastrointestinal toxicity was noted. Acute grade 2 genitourinary and gastrointestinal toxicities were 8.3% and 11.7%, respectively. Late grade 2 genitourinary and gastrointestinal toxicities were 3.3% and 8.3%, respectively. Late grade 3 genitourinary toxicity was seen in two (3.3%) patients. Three-year overall survival and biochemical failure-free survival was 89% and 77%, respectively.ConclusionSBRT to the prostate and pelvis is safe and efficacious in node-positive prostate cancer even with common iliac nodal involvement (stage M1a). 相似文献
973.
974.
Anupam Kotwal Alejandro Ferrer Rajiv Kumar Ravinder J Singh Vishakantha Murthy Laura Schultz-Rogers Michael Zimmermann Brendan Lanpher Kristin Zimmerman Paul R Stabach Eric Klee Demetrios T Braddock Robert A Wermers 《Journal of bone and mineral research》2020,35(4):662-670
Inactivating mutations of the ENPP1 gene are associated with generalized arterial calcification of infancy (GACI) and less often autosomal-recessive hypophosphatemic rickets type 2 (ARHR2). We aimed to investigate the spectrum of phenotypes in a family with monoallelic and biallelic mutations of ENPP1 after identification through whole exome sequencing of a 54-year-old female with biallelic mutation of ENPP1, c.323G > T; p.Cys108Phe and c.1441C > T; p.Arg481Trp. Including the proband, 2 subjects had biallelic mutations, 5 had monoallelic mutations, and 2 had no mutation of ENPP1. The maternal mutation, a known pathogenic variant associated with GACI, was found in 3 subjects with monoallelic mutations, while the paternal mutation, which was not previously reported, was present in 2 subjects with monoallelic mutations. Both subjects with biallelic mutations had bowing of bilateral femurs, periarticular mineral deposition, normocalcemic primary hyperparathyroidism with multigland parathyroidectomy, increased carotid intima-media thickness, and enthesopathy was also noted in one subject. Intact FGF23 was elevated in both subjects with biallelic mutations, while C-terminal FGF23 was only elevated in one and PPi was reduced in one. Subjects with monoallelic mutations did not have periarticular calcifications or bone deformities. To conclude, patients with biallelic GACI causing mutations can survive well into adulthood, and despite the same biallelic ENPP1 pathogenic variants, clinical and biochemical manifestations can significantly differ, and include enthesopathy and primary hyperparathyroidism, which have not been previously described. Although carriers of monoallelic ENPP1 variants appear unaffected by classic disease manifestations, there may be subtle biochemical and clinical findings that warrant further investigation. © 2019 American Society for Bone and Mineral Research. 相似文献
975.
J N Murthy Y Chen V S Warty R Venkataramanan J G Donnelly A Zeevi S J Soldin 《Clinical chemistry》1992,38(7):1307-1310
We describe a quantitative radioreceptor assay (RRA) for quantifying FK-506 in whole blood. FK-506 extracted from whole blood with a cyclohexyl-sorbent column competes with [3H]dihydro-FK-506 for binding to a partially purified preparation of FK-506 binding protein (FK-BP). Free and protein-bound FK-506 are separated on LH 20 Sephadex chromatographic columns. We compared the results of this method with those of an enzyme immunoassay that uses a monoclonal antibody: r = 0.97, Sy/x = 0.039. Between-day precisions (CV) at FK-506 concentrations of 8 and 17 micrograms/L were 9.2% and 8.2%, respectively. Within-run precisions were 5.9%, 8.1%, and 9.4%, respectively, at 4, 8, and 15 micrograms/L. Analytical recovery, evaluated at 5, 10, 15, 20, and 25 micrograms/L for FK-506 added to whole blood, ranged from 98% to 103%. The assay can reliably quantify FK-506 blood concentrations between 1.0 and 25 micrograms/L. 相似文献
976.
977.
Marcus J. Schultz Martin W. Dunser Arjen M. Dondorp Neill K. J. Adhikari Shivakumar Iyer Arthur Kwizera Yoel Lubell Alfred Papali Luigi Pisani Beth D. Riviello Derek C. Angus Luciano C. Azevedo Tim Baker Janet V. Diaz Emir Festic Rashan Haniffa Randeep Jawa Shevin T. Jacob Niranjan Kissoon Rakesh Lodha Ignacio Martin-Loeches Ganbold Lundeg David Misango Mervyn Mer Sanjib Mohanty Srinivas Murthy Ndidiamaka Musa Jane Nakibuuka Ary Serpa Neto Mai Nguyen Thi Hoang Binh Nguyen Thien Rajyabardhan Pattnaik Jason Phua Jacobus Preller Pedro Povoa Suchitra Ranjit Daniel Talmor Jonarthan Thevanayagam C. Louise Thwaites For the Global Intensive Care Working Group of the European Society of Intensive Care Medicine 《Intensive care medicine》2017,43(5):612-624
978.
979.
Hamblin MR O'Donnell DA Murthy N Rajagopalan K Michaud N Sherwood ME Hasan T 《The Journal of antimicrobial chemotherapy》2002,49(6):941-951
OBJECTIVES: We have shown previously that a polycationic conjugate between poly-L-lysine and the photosensitizer chlorin(e6) was effective in photodynamic inactivation (PDI) of both Gram-positive and Gram-negative bacteria. In this report we explore the relationship between the size of the polylysine chain and its effectiveness for mediating the killing of Gram-negative and Gram-positive bacteria. METHODS: Conjugates were prepared by attaching precisely one chlorin(e6) molecule to the alpha-amino group of poly-(epsilon-benzyloxycarbonyl)lysines of average length eight and 37 lysine residues, followed by deprotection of the epsilon-amino groups, and were characterized by iso-electric focusing. The uptake of these conjugates and free chlorin(e6) by Gram-positive Staphylococcus aureus (ATCC 27659) and Gram-negative Escherichia coli (ATCC 29181) after washing was measured as a function of photosensitizer concentration (0-4 microM chlorin(e6) equivalent) and incubation time. After incubation the bacteria were exposed to low fluences (10-40 J/cm(2)) of 660 nm light delivered from a diode laser, and viability was assessed after serial dilutions by a colony-forming assay. RESULTS: S. aureus and E. coli took up comparable amounts of the two conjugates, but free chlorin(e6) was only taken up by S. aureus. After illumination S. aureus was killed in a fluence-dependent fashion when loaded with the 8-lysine conjugate and free chlorin(e6) but somewhat less so with the 37-lysine conjugate. In contrast, PDI of E. coli was only effective with the 37-lysine conjugate at concentrations up to 4 microM. PDI using the 8-lysine conjugate and free chlorin(e6) on E. coli was observed at a concentration of 100 microM. Transmission electron micrographs showed internal electron-lucent areas consistent with chromosomal damage. CONCLUSION: These results can be explained by the necessity of a large polycation to penetrate the impermeable outer membrane of Gram-negative E. coli, while Gram-positive S. aureus is more easily penetrated by small molecules. However, because S. aureus is more sensitive overall than E. coli the 37-lysine conjugate can effectively kill both bacteria. 相似文献
980.
Atwell Thomas D. Wennberg Paul W. McMenomy Brendan P. Murthy Naveen S. Anderson Jeremy R. Kriegshauser J. Scott McKinney J. Mark 《Abdominal imaging》2017,42(5):1556-1565
Abdominal Radiology - Peri-procedural anticoagulant management hinges on the balance of hemorrhagic and thrombotic complications. The radiologist is tasked with accurately assessing the hemorrhagic... 相似文献