全文获取类型
收费全文 | 177篇 |
免费 | 9篇 |
国内免费 | 26篇 |
专业分类
耳鼻咽喉 | 11篇 |
儿科学 | 10篇 |
妇产科学 | 2篇 |
基础医学 | 12篇 |
临床医学 | 30篇 |
内科学 | 29篇 |
神经病学 | 13篇 |
特种医学 | 3篇 |
外科学 | 11篇 |
综合类 | 4篇 |
预防医学 | 18篇 |
眼科学 | 11篇 |
药学 | 46篇 |
肿瘤学 | 12篇 |
出版年
2022年 | 2篇 |
2021年 | 1篇 |
2020年 | 1篇 |
2019年 | 4篇 |
2018年 | 6篇 |
2017年 | 3篇 |
2015年 | 3篇 |
2014年 | 8篇 |
2013年 | 9篇 |
2012年 | 9篇 |
2011年 | 8篇 |
2010年 | 5篇 |
2009年 | 2篇 |
2008年 | 7篇 |
2007年 | 21篇 |
2006年 | 2篇 |
2005年 | 5篇 |
2004年 | 2篇 |
2003年 | 2篇 |
2002年 | 2篇 |
2001年 | 3篇 |
2000年 | 12篇 |
1999年 | 6篇 |
1998年 | 10篇 |
1997年 | 11篇 |
1996年 | 6篇 |
1995年 | 6篇 |
1993年 | 2篇 |
1992年 | 5篇 |
1991年 | 8篇 |
1990年 | 7篇 |
1989年 | 12篇 |
1988年 | 7篇 |
1985年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1965年 | 1篇 |
1961年 | 1篇 |
1960年 | 1篇 |
排序方式: 共有212条查询结果,搜索用时 15 毫秒
1.
吡酮酸类抗菌药物的研究Ⅷ.1-对氟苯基-6-氟-1,4-二氢-4-氧-7-(1-哌嗪)噌啉-3-羧酸及其类似物的合成和构效关系 总被引:1,自引:0,他引:1
为探讨构效关系,合成了1-对氟苯基-6-氟-1,4-二氢-4-氧-7-(1-哌嗪)噌啉-3-羧酸及其喹啉、萘啶、吡啶[2,3-C]哒嗪环系类似物16个。测定了对大肠杆菌的MIC。用Hückel分子轨道理论(HMO)方法计算了四个母体环上电子密度。结果表明:环中氮的位置对药效团——3位羧基和4位羰基氧原子上电子密度的影响较大而影响其抗菌活性。喹啉、萘啶两环系的3位羧基和4位羰基氧原子上的电子密度较高,其体外抗菌活性较高;而噌啉及吡啶[2,3-C]哒嗪两环系的电子密度较低,其体外抗菌活性较低甚至消失。 相似文献
2.
Van de Velde H; De Vos A; Joris H; Nagy ZP; Van Steirteghem AC 《Human reproduction (Oxford, England)》1998,13(11):3160-3164
In human in-vitro fertilization (IVF), the oocytes are surrounded by
cumulus and corona cells at the time of insemination so that their maturity
cannot easily be evaluated. The best IVF results are obtained if the
oocytes are inseminated 2-6 h after retrieval. In the intracytoplasmic
sperm injection (ICSI) procedure, the oocytes are denuded by enzymatic and
mechanical treatment in order to be able to perform the injection. As a
consequence, the nuclear maturity of the oocytes can be evaluated and only
those that have extruded the first polar body are injected. However,
metaphase-II oocytes that have not yet reached cytoplasmic maturity cannot
be recognized. The purpose of this study was to investigate the effect of
different timing of cumulus- corona cell removal and injection on the
outcome of ICSI. For this we allowed the oocytes to complete in-vitro
cytoplasmic maturation in two different culture conditions: (i) surrounded
by their cumulus and corona cells or (ii) totally denuded. We performed
three different studies on sibling oocytes obtained after a standardized
buserelin/human menopausal gonadotrophin (HMG) protocol. We investigated
the effect of early (1-2 h after retrieval) and late (5-6 h after
retrieval) oocyte denudation and injection on the survival and
fertilization of the injected oocytes and on embryo cleavage after
fertilization. We found no statistically significant differences between
early and late injection, indicating that after a standardized
buserelin/HMG protocol the metaphase-II oocytes do not need time for
further cytoplasmic maturation. Furthermore, a different timing of
cumulus-corona cell removal has no effect on the outcome of ICSI,
suggesting that the surrounding cells are not necessary for survival,
fertilization and cleavage after ICSI.
相似文献
3.
Percoll gradient centrifugation can be omitted in sperm preparation for intracytoplasmic sperm injection 总被引:4,自引:3,他引:4
De Vos A; Nagy ZP; Van de Velde H; Joris H; Bocken G; Van Steirteghem A 《Human reproduction (Oxford, England)》1997,12(9):1980-1984
Prior to intracytoplasmic sperm injection (ICSI), seminal fluid is
currently washed out from the ejaculated semen and further sperm selection
is carried out by a discontinuous Percoll gradient. Possible deleterious
effects from the sperm-separating substance Percoll on sperm function or
embryo cleavage after in-vitro fertilization (IVF) have, to our knowledge,
not yet been reported and the use of Percoll has been widely accepted in
IVF. In this study, we examined whether the omission of the Percoll step in
the sperm preparation has any influence on the outcome of the ICSI
procedure. Two methods of sperm preparation for ICSI were compared in a
controlled study on sibling oocytes: washing the semen sample once,
followed by a Percoll gradient centrifugation versus washing the sperm
sample twice without a Percoll gradient centrifugation. The mean
fertilization rates were similar for the two sperm preparation methods:
78.2 +/- 21.4 and 75.0 +/- 24.1% respectively of the intact oocytes
displaying two pronuclei. Cleavage rates did not differ statistically
between the two groups. Whereas in both groups similar percentages of
excellent, good and poor quality embryos were obtained, the percentage of
fair quality embryos was significantly higher in the group without Percoll
(16.3 +/- 20.1 versus 9.1 +/- 15.7%). However, no statistical differences
were observed in either the percentage of transferable embryos or in the
percentage of embryos actually transferred or frozen in the two groups. In
conclusion, spermatozoa from ejaculates that are washed out from the
seminal fluid without any further selection can be used for ICSI without
any adverse effect on fertilization and embryo cleavage.
相似文献
4.
5.
Summary Impaired -6 essential fatty acid metabolism and exaggerated polyol pathway flux contribute to the neurovascular abnormalities in streptozotocin-diabetic rats. The potential interactions between these mechanisms were examined by comparing the effects of threshold doses of aldose reductase inhibitors and evening primrose oil, alone and in combination, on neurovascular deficits. In addition, highdose aldose reductase inhibitor and evening primrose oil treatment effects were challenged by co-treatment with the cyclo-oxygenase inhibitor, flurbiprofen, or the nitric oxide synthase inhibitor, NG-nitro-l-arginine. Eight weeks of diabetes caused an 18.9% reduction in sciatic motor conduction velocity (p<0.001). This was only modestly ameliorated by a 0.1% dietary supplement of evening primrose oil or the aldose reductase inhibitors ZD5522 (0.25 mg · kg–1 · day–1) and WAY121509 (0.2 mg · kg–1· day–1) for the final 2 weeks. However, joint treatment with primrose oil and ZD5522 or WAY121509 caused marked 71.5 and 82.4% corrections, respectively, of the conduction deficit. Sciatic nutritive blood flow was 43.1% reduced by diabetes (p<0.001) and this was corrected by 67.8% with joint ZD5522 and primrose oil treatment (p<0.001). High-dose WAY121509 (10 mg · kg–1 · day–1) and primrose oil (10% dietary supplement) prevented sciatic conduction velocity and nutritive blood flow deficits in 1-month diabetic rats (p<0.001). However, these effects were abolished by flurbiprofen (5 mg · kg–1 · day–1) and NG-nitro-l-arginine (10 mg · kg–1 · day–1) co-treatment (p<0.001). Thus, the data provide evidence for synergistic interactions between polyol pathway/nitric oxide and essential fatty acid/cyclo-oxygenase systems in the control of neurovascular function in diabetic rats, from which a potential therapeutic advantage could be derived.Abbreviations ARI
Aldose reductase inhibitor
- EPO
evening primrose oil
- NCV
nerve conduction velocity
- NO
nitric oxide
- NOLA
NG-nitro-l-arginine 相似文献
6.
Summary Aldose reductase inhibitors (ARIs) attenuate diabetic complications in several tissues, including lens, retina, kidney, blood
vessels, striated muscle and peripheral nerve. However, it is unclear whether their action in diabetes mellitus depends directly
on inhibiting the conversion of glucose to sorbitol by aldose reductase or indirectly by reducing the sorbitol available for
subsequent metabolism to fructose by sorbitol dehydrogenase. To identify the polyol pathway step most relevant to complications,
particularly neuropathy, we compared the biochemical effects of a sorbitol dehydrogenase inhibitor, WAY-135 706, (250 mg ·
kg−1· day−1) and an ARI, WAY-121 509, (10 mg · kg−1· day−1) on a variety of tissues, and their effects on nerve perfusion and conduction velocity. After 6 weeks of untreated streptozotocin
diabetes, rats were treated for 2 weeks. Sorbitol was elevated 2.1–32.6-fold by diabetes in lens, retina, kidney, aorta, diaphragm,
erythrocytes and sciatic nerve; this was further increased (1.6–8.2-fold) by WAY-135 706 whereas WAY-121 509 caused a marked
reduction. Fructose 1.6–8.0-fold elevated by diabetes in tissues other than diaphragm, was reduced by WAY-135 706 and WAY-121
509, except in the kidney. Motor and sensory nerve conduction velocities were decreased by 20.2 and 13.9 %, respectively with
diabetes. These deficits were corrected by WAY-121 509, but WAY-135 706 was completely ineffective. A 48.6 % diabetes-induced
deficit in sciatic nutritive endoneurial blood flow was corrected by WAY-121 509, but was unaltered by WAY-135 706. Thus,
despite profound sorbitol dehydrogenase inhibition, WAY-135 706 had no beneficial effect on nerve function. The data demonstrate
that aldose reductase activity, the first step in the polyol pathway, makes a markedly greater contribution to the aetiology
of diabetic neurovascular and neurological dysfunction than does the second step involving sorbitol dehydrogenase. [Diabetologia
(1997) 40: 271–281]
Received: 13 August 1996 and in final revised form: 6 December 1996 相似文献
7.
8.
In response to growing interest in employing behavioral treatments and environmental modification for behavioral disturbances in older adults, we employed vignette methodology to examine physicians' acceptance of two behavioral treatments and haloperidol using Kazdin's Treatment Evaluation Inventory. Physicians assigned the highest acceptability ratings to the behavioral treatments and the lowest ratings to haloperidol. The patient's cognitive capacity, living situation (nursing home vs. community), and the type of behavior problem mediated treatment acceptability ratings. 相似文献
9.
10.
High glucose-induced mesangial cell altered contractility: role of the polyol pathway 总被引:2,自引:0,他引:2
B. Derylo T. Babazono E. Glogowski J. Kapor-Drezgic T. Hohman C. Whiteside 《Diabetologia》1998,41(5):507-515
Summary Glomerular mesangial cells cultured in high glucose conditions display impaired contractile responsiveness. It was postulated
that glucose metabolism through the polyol pathway leads to altered mesangial cell contractility involving protein kinase
C. Rat mesangial cells were growth-arrested for 24 h with 0.5 % fetal bovine serum in either normal (5.6 mmol/l) or high (30
mmol/l) glucose concentrations or high glucose plus the aldose reductase inhibitor, ARI-509 (100 μmol/l). The reduction of
cell planar surface area (contraction) in response to endothelin-1 (0.1 μmol/l), or to phorbol 12-myristate 13-acetate (50
pmol/l), was studied by videomicroscopy. In response to endothelin-1, mesangial cells in normal glucose contracted to 52 ±
3 % of initial planar area. In high glucose, the significantly (p < 0.05) smaller cell size and no contractile responsiveness to endothelin-1 were normalized with ARI-509. Membrane-associated
diacylglycerol, measured by a kinase specific 32P-phosphorylation assay, in high glucose was unchanged after 3 h, but significantly increased (p < 0.05) after 24 h which was normalized with ARI-509. Protein kinase C activity, measured by in situ 32P-phosphorylation of the epidermal growth factor receptor substrate was: increased by 32 % at 3 h of high glucose, unchanged
by ARI-509; and decreased significantly (p < 0.05) at 24 h compared to cells in normal glucose, normalized by ARI-509. Total cellular protein kinase C-alpha, -delta
and -epsilon, analysed by immunoblotting, were unchanged in high glucose at 24 h. Only protein kinase C-epsilon content was
reduced by ARI-509 in both normal and high glucose. Therefore, high glucose-induced loss of mesangial cell contractility,
diacylglycerol accumulation and altered protein kinase C activity are mediated through activation of the polyol-pathway, although
no specific relationship between elevated diacylglycerol and protein kinase C activity was observed. In high glucose, altered
protein kinase C function, or another mechanism related to the polyol pathway, contribute to loss of mesangial cell contractile
responsiveness. [Diabetologia (1998) 41: 507–515]
Received: 18 July 1997 and in final revised form: 17 January 1998 相似文献