全文获取类型
收费全文 | 149篇 |
免费 | 10篇 |
国内免费 | 5篇 |
专业分类
儿科学 | 9篇 |
妇产科学 | 1篇 |
基础医学 | 25篇 |
口腔科学 | 3篇 |
临床医学 | 15篇 |
内科学 | 28篇 |
皮肤病学 | 6篇 |
神经病学 | 2篇 |
特种医学 | 44篇 |
外科学 | 2篇 |
综合类 | 3篇 |
预防医学 | 8篇 |
眼科学 | 2篇 |
药学 | 13篇 |
肿瘤学 | 3篇 |
出版年
2021年 | 4篇 |
2020年 | 2篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2015年 | 4篇 |
2014年 | 4篇 |
2013年 | 4篇 |
2012年 | 3篇 |
2011年 | 4篇 |
2010年 | 10篇 |
2009年 | 1篇 |
2008年 | 2篇 |
2007年 | 1篇 |
2006年 | 7篇 |
2005年 | 3篇 |
2002年 | 1篇 |
2001年 | 3篇 |
1999年 | 4篇 |
1998年 | 13篇 |
1997年 | 8篇 |
1996年 | 13篇 |
1995年 | 6篇 |
1994年 | 7篇 |
1993年 | 7篇 |
1992年 | 4篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 2篇 |
1978年 | 4篇 |
1977年 | 9篇 |
1976年 | 2篇 |
1975年 | 2篇 |
排序方式: 共有164条查询结果,搜索用时 15 毫秒
101.
102.
Decreased nucleotide and serotonin storage associated with defective function in Chediak-Higashi syndrome cattle and human platelets 总被引:5,自引:0,他引:5
Prolonged mean template bleeding time of 14 min observed in seven cattle with the Chediak-Higashi syndrome (CHS) prompted the examination of platelet function in these animals. There was no distinguishable difference in concentration of circulating platelets between CHS and control cattle. CHS bovine platelets failed to aggregate in vitro in response to concentrations of acid-soluble collagen which induced aggregation in all normal samples. The primary platelet response to 5 muM ADP was normal in CHS cattle. A markedly decreased amount of serotonin (1.2% of normal) was detected in CHS bovine platelets. Bovine CHS platelet ATP and ADP contents were significantly less than normal, and the ATP/ADP ratios were 5.04 in normal and 29.38 in CHS platelets. Results of these animal investigations prompted a similar study of two patients with CHS. In humans, an increased bleeding time greater than 15 min and an in vitro impaired aggregation response to acid-soluble collagen and 5 muM adrenaline were discovered. Both ATP and ADP were reduced in CHS human platelets, and the ATP/ADP ratio was 3.96, compared to a ratio of 1.52 for platelets of two normal subjects. These findings suggested the presence of a "storage pool disease" of CHS platelets. 相似文献
103.
Studies of the survival time of 51Cr labeled erythrocytes treated in vitro with methyl acetimidate (MAI) were conducted in 13 patients with sickle cell disease in order to assess the suitability of this antisickling agent for more extensive clinical testing. In comparison with previously measured control values (average t1/2 8.4 +/- 1.1 days a), the survival time of the treated erythrocytes in 10 of the patients who were not transfused was initially prolonged (average t1/2 24.4 +/- 4.6 days). However, 5 of the 13 patients studied developed circulating antibody against the MAI treated erythrocytes, markedly reducing the survival time of MAI treated erythrocytes in subsequent studies. Two patients, each challenged 3 times with infused MAI treated erythrocytes, failed to show evidence of antibody production, suggesting that not all subjects become immunized even after repeated exposure. In spite of many other promising properties of MAI as an antisickling agent of potential value, consideration of its use in further clinical testing must depend on successful avoidance of immunization in patients receiving infusions of treated erythrocytes. 相似文献
104.
Rapid deactivation of NADPH oxidase in neutrophils: continuous replacement by newly activated enzyme sustains the respiratory burst 总被引:6,自引:0,他引:6
The cell-free system for activation of the neutrophil NADPH oxidase allowed us to examine activation of the oxidase in the absence of its NADPH-dependent turnover. The covalent sulfhydryl-modifying reagent N- ethylmaleimide completely inhibited the activation step (Ki = 40 mumol/L) in the cell-free system but had no effect on turnover of the preactivated particulate NADPH oxidase (up to 1 mmol/L). When N- ethylmaleimide was added to intact neutrophils during the period of maximal O2 generation in response to stimuli that activate the respiratory burst (phorbol myristate acetate, f-Met-Leu-Phe, opsonized zymosan, arachidonic acid), O2- generation ceased within seconds. Study of components of the cell-free activation system indicated that the cytosolic cofactor was irreversibly inhibited by N-ethylmaleimide whereas the N-ethylmaleimide-treated, membrane-associated oxidase could be activated by arachidonate and control cytosolic cofactor. Likewise, the cell-free system prepared from intact neutrophils that had been briefly exposed to N-ethylmaleimide and then washed reflected the effects of N-ethylmaleimide on the isolated cell-free components: cytosolic cofactor activity was absent, but the membrane oxidase remained fully activatable. Thus inhibition of oxidase activation by N- ethylamaleimide unmasked a rapid deactivation step that was operative in intact neutrophils but not in isolated particulate NADPH oxidase preparations. The demonstrated specificity of N-ethylmaleimide for oxidase activation and lack of effect on turnover of the NADPH oxidase suggested that sustained O2- generation by intact neutrophils was a result of continued replenishment of a small pool of active oxidase. The existence of an inactive pool of NADPH oxidase molecules in particulate preparations from stimulated neutrophils was supported more directly by activating these preparations again in the cell-free system. 相似文献
105.
Parks NJ; Kawakami TG; Avila MJ; White R; Cain GR; Raaka SD; Hornoff W; Fisher P; Moore P; Seibert JA 《Blood》1993,82(1):318-325
beta-emitting 166Ho (t1/2 = 26.78 hours, E(beta)max = 1.8 MeV) complexed with the phosphonic acid chelator, 1,4,7,10 tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid) (DOTMP) at a ligand-to-metal ratio of 1.5:1 binds to bone. This radioactive complex is a marrow-ablating radiopharmaceutical that appears useful for preparation of bone marrow (BM) transplant recipients without the morbidity usually associated with total body irradiation preparatory regimens. We have found with seven splenectomized young adult beagle dogs that a 166Ho radiopharmaceutical dosage of 370 MBq/kg body weight provides an initial skeletal radioactivity burden of at least 1.5 GBq/kg skeleton and results in complete ablation of hematopoietic marrow cell populations within 7 days. The beta particle flux distribution in BM-forming skeletal tissue is not uniform. Red marrow radiation doses varied from 30 to 115 Gy as estimated by direct radioassay and autoradiographic analyses of both bone biopsies and postmortem samples; the median value of 61 Gy agreed with our theoretical expectations. In vivo radioactivity distribution was evaluated with nuclear imaging methods. Apparently, normal hematopoiesis was restored in three dogs with autologous BM transplants performed 5 to 6 days after administration of the marrow ablative radiopharmaceutical, 166Ho-DOTMP. BM biopsies at 7 to 10 months posttransplantation indicate continued normal hematopoietic activity. 相似文献
106.
Mycobacterium tuberculosis dysregulates MMP/TIMP balance to drive rapid cavitation and unrestrained bacterial proliferation 下载免费PDF全文
André Kübler Brian Luna Christer Larsson Nicole C Ammerman Bruno B Andrade Marlene Orandle Kevin W Bock Ziyue Xu Ulas Bagci Daniel J Mollura John Marshall Jay Burns Kathryn Winglee Bintou Ahmadou Ahidjo Laurene S Cheung Mariah Klunk Sanjay K Jain Nathella Pavan Kumar Subash Babu Alan Sher Jon S Friedland Paul TG Elkington William R Bishai 《The Journal of pathology》2015,235(3):431-444
Active tuberculosis (TB) often presents with advanced pulmonary disease, including irreversible lung damage and cavities. Cavitary pathology contributes to antibiotic failure, transmission, morbidity and mortality. Matrix metalloproteinases (MMPs), in particular MMP‐1, are implicated in TB pathogenesis. We explored the mechanisms relating MMP/TIMP imbalance to cavity formation in a modified rabbit model of cavitary TB. Our model resulted in consistent progression of consolidation to human‐like cavities (100% by day 28), with resultant bacillary burdens (>107 CFU/g) far greater than those found in matched granulomatous tissue (105 CFU/g). Using a novel, breath‐hold computed tomography (CT) scanning and image analysis protocol, we showed that cavities developed rapidly from areas of densely consolidated tissue. Radiological change correlated with a decrease in functional lung tissue, as estimated by changes in lung density during controlled pulmonary expansion (R2 = 0.6356, p < 0.0001). We demonstrated that the expression of interstitial collagenase (MMP‐1) was specifically greater in cavitary compared to granulomatous lesions (p < 0.01), and that TIMP‐3 significantly decreased at the cavity surface. Our findings demonstrated that an MMP‐1/TIMP imbalance is associated with the progression of consolidated regions to cavities containing very high bacterial burdens. Our model provided mechanistic insight, correlating with human disease at the pathological, microbiological and molecular levels. It also provided a strategy to investigate therapeutics in the context of complex TB pathology. We used these findings to predict a MMP/TIMP balance in active TB and confirmed this in human plasma, revealing the potential of MMP/TIMP levels as key components of a diagnostic matrix aimed at distinguishing active from latent TB (PPV = 92.9%, 95% CI 66.1–99.8%, NPV = 85.6%; 95% CI 77.0–91.9%). Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd 相似文献
107.
Distinct mutation patterns of breast cancer-associated alleles of the HRAS1 minisatellite locus 总被引:1,自引:0,他引:1
DNA sequence analysis of 130 alleles of the HRAS1 minisatellite has
demonstrated that breast cancer-associated variants arise as a consequence
of both replication errors and gene conversions. Unlike mutations at other
variable number of tandem repeats (VNTRs), high-risk variants of the HRAS1
minisatellite do not demonstrate positional polarity. Instead, most
mutations occur at three hotspots, with replication errors confined to one
hotspot, gene conversions to a second and a mixed pattern of mutation at
the third. DNA sequence analysis of 66 low-risk a1 alleles revealed no
evidence for hypermutation. Therefore, while the HRAS1 minisatellite may
serve as a reporter for a broad-based group of mutational mechanisms, these
results are consistent with a direct pathogenetic contribution by high-
risk alleles as the biological basis underlying cancer association of this
VNTR.
相似文献
108.
Handelsman DJ Cooper TG 《国外医学(计划生育.生殖健康分册)》2010,29(3):133-135
精液分析成为不育研究的重要部分经历了一个极其漫长的历史变迁过程,并声名狼藉,曾经被排除在常规的病理学检查之外,直到近些年才引起学术界的重视。精液分析起源于19世纪,那时对精子的认识仅仅局限于检测性交后宫颈黏液中是否存在精子,曾认为是“有失体面的,不自重的^[1]。” 相似文献
109.
Automatic motion correction for breast MR imaging 总被引:2,自引:0,他引:2