全文获取类型
收费全文 | 505篇 |
免费 | 48篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 39篇 |
妇产科学 | 10篇 |
基础医学 | 73篇 |
口腔科学 | 30篇 |
临床医学 | 44篇 |
内科学 | 113篇 |
皮肤病学 | 22篇 |
神经病学 | 6篇 |
特种医学 | 60篇 |
外科学 | 38篇 |
综合类 | 32篇 |
预防医学 | 45篇 |
药学 | 22篇 |
1篇 | |
肿瘤学 | 14篇 |
出版年
2021年 | 4篇 |
2018年 | 5篇 |
2017年 | 3篇 |
2016年 | 9篇 |
2015年 | 22篇 |
2014年 | 16篇 |
2013年 | 19篇 |
2012年 | 13篇 |
2011年 | 13篇 |
2010年 | 24篇 |
2009年 | 11篇 |
2008年 | 12篇 |
2007年 | 12篇 |
2006年 | 10篇 |
2005年 | 20篇 |
2004年 | 10篇 |
2003年 | 9篇 |
2002年 | 5篇 |
2001年 | 13篇 |
2000年 | 7篇 |
1999年 | 10篇 |
1998年 | 21篇 |
1997年 | 19篇 |
1996年 | 29篇 |
1995年 | 15篇 |
1994年 | 22篇 |
1993年 | 14篇 |
1992年 | 11篇 |
1991年 | 8篇 |
1990年 | 17篇 |
1989年 | 9篇 |
1988年 | 23篇 |
1987年 | 8篇 |
1986年 | 10篇 |
1985年 | 16篇 |
1984年 | 9篇 |
1983年 | 12篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1977年 | 8篇 |
1976年 | 4篇 |
1975年 | 3篇 |
1972年 | 3篇 |
1971年 | 3篇 |
1970年 | 3篇 |
1967年 | 3篇 |
1965年 | 3篇 |
排序方式: 共有554条查询结果,搜索用时 78 毫秒
1.
Golli M; Van Nhieu JT; Mathieu D; Zafrani ES; Cherqui D; Dhumeaux D; Vasile N; Rahmouni A 《Radiology》1994,190(3):741
2.
3.
4.
5.
Inhibition of 2-nitropropane-induced rat liver DNA and RNA damage by benzyl selenocyanate 总被引:5,自引:2,他引:3
We observed that pretreatment of male F344 rats with benzyl selenocyanate,
a versatile organoselenium chemopreventive agent in several animal model
systems, decreases the levels of DNA and RNA modifications produced in the
liver by the hepatocarcinogen 2- nitropropane. To clarify the mechanisms
involved, we pretreated male F344 rats with either benzyl selenocyanate,
its sulfur analog benzyl thiocyanate, phenobarbital or cobalt
protoporphyrin IX; the latter is a depletor of P450. We then determined (1)
the ability of liver microsomes to denitrify 2-nitropropane, (2) effects on
2-nitropropane- induced liver DNA and RNA modifications and (3) amount of
nitrate excreted in rat urine following administration of the carcinogen.
Pretreatment with benzyl selenocyanate or phenobarbital increased the
denitrification activity of liver microsomes by 217 and 765%, respectively,
increased liver P4502B1 by 31- and 435-fold, respectively, decreased the
levels of 2-nitropropane-induced modifications in liver DNA (29-70% and
17-30%, respectively) and RNA (67-85% and 30-50%, respectively), and
increased the 24-h urinary excretion of nitrate by 157 and 209%,
respectively. Pretreatment with benzyl thiocyanate had no significant
effect on any of these parameters. Pretreatment with cobalt protoporphyrin
IX decreased liver P4502B 1 by 87%, decreased the denitrification activity
of liver microsomes by 76%, decreased the 24 h urinary excretion of nitrate
by 88.5%, but increased the extent of 2-nitropropane-induced liver nucleic
acid modifications by 17-67%. These results indicate that the metabolic
sequence from 2-nitropropane to the reactive species causing DNA and RNA
modifications does not involve the removal of the nitro group. Moreover,
they suggest that benzyl selenocyanate inhibits 2-NP-induced liver nucleic
acid modifications in part by increasing its detoxication through induction
of denitrification, although it is evident that other mechanisms must also
be involved.
相似文献
6.
7.
Overexpression of monocyte chemotactic protein-1/CCL2 in beta-amyloid precursor protein transgenic mice show accelerated diffuse beta-amyloid deposition
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Yamamoto M Horiba M Buescher JL Huang D Gendelman HE Ransohoff RM Ikezu T 《The American journal of pathology》2005,166(5):1475-1485
Microglia accumulation at the site of amyloid plaques is a strong indication that microglia play a major role in Alzheimer's disease pathogenesis. However, how microglia affect amyloid-beta peptide (Abeta) deposition remains poorly understood. To address this question, we developed a novel bigenic mouse that overexpresses both amyloid precursor protein (APP) and monocyte chemotactic protein-1 (MCP-1; CCL2 in systematic nomenclature). CCL2 expression, driven by the glial fibrillary acidic protein promoter, induced mononuclear phagocyte (MP; monocyte-derived macrophage and microglial) accumulation in the brain. When APP/CCL2 transgenic mice were compared to APP mice, a fivefold increase in Abeta deposition was present despite increased MP accumulation around hippocampal and cortical amyloid plaques. Levels of full-length APP, its C-terminal fragment, and Abeta-degrading enzymes (insulin-degrading enzyme and neprilysin) in APP/CCL2 and APP mice were indistinguishable. Sodium dodecyl sulfate-insoluble Abeta (an indicator of fibrillar Abeta) was increased in APP/CCL2 mice at 5 months of age. Apolipoprotein E, which enhances Abeta deposition, was also increased (2.2-fold) in aged APP/CCL2 as compared to APP mice. We propose that although CCL2 stimulates MP accumulation, it increases Abeta deposition by reducing Abeta clearance through increased apolipoprotein E expression. Understanding the mechanisms underlying these events could be used to modulate microglial function in Alzheimer's disease and positively affect disease outcomes. 相似文献
8.
A model of corrective gene transfer in X-linked ichthyosis 总被引:5,自引:0,他引:5
Freiberg RA; Choate KA; Deng H; Alperin ES; Shapiro LJ; Khavari PA 《Human molecular genetics》1997,6(6):927-933
Single gene recessive genetic skin disorders offer attractive prototypes
for the development of therapeutic cutaneous gene delivery. We have
utilized X-linked ichthyosis (XLI), characterized by loss of function of
the steroid sulfatase arylsulfatase C (STS), to develop a model of
corrective gene delivery to human skin in vivo. A new retroviral expression
vector was produced and utilized to effect STS gene transfer to primary
keratinocytes from XLI patients. Transduction was associated with
restoration of full-length STS protein expression as well as steroid
sulfatase enzymatic activity in proportion to the number of proviral
integrations in XLI cells. Transduced and uncorrected XLI keratinocytes,
along with normal controls, were then grafted onto immunodeficient mice to
regenerate full thickness human epidermis. Unmodified XLI keratinocytes
regenerated a hyperkeratotic epidermis lacking STS expression with
defective skin barrier function, effectively recapitulating the human
disease in vivo. Transduced XLI keratinocytes from the same patients,
however, regenerated epidermis histologically indistinguishable from that
formed by keratinocytes from patients with normal skin. Transduced XLI
epidermis demonstrated STS expression in vivo by immunostaining as well as
a normalization of histologic appearance at 5 weeks post-grafting. In
addition, transduced XLI epidermis demonstrated a return of barrier
function parameters to normal. These findings demonstrate corrective gene
delivery in human XLI patient skin tissue at both molecular and functional
levels and provide a model of human cutaneous gene therapy.
相似文献
9.
A. KIJLSTRA D. W. KNUTSON M. R. DAHA L. A. VAN ES 《Scandinavian journal of immunology》1979,10(5):421-429
The in vivo behaviour of well-defined immune complexes in rats was studied using complexes derived from DNP-conjugated bovine thyroglobulin (DNP-BTG) and purified specific goat anti-DNP IgG. Both clearance and glomerular localization were mainly dependent on the nature of the antigen. Soluble immune complexes formed with DNP17-BTG were cleared faster and showed a more marked localization in the glomerular mesangium than complexes formed with DNP3.4-BTG. A slight increase in the antibody to antigen ratio seemed to facilitate mesangial localization of soluble immune complexes. Insoluble immune complexes showed temporary localization as microemboli in the lumina of glomerular and peritubular capillaries. This study thus shows that not only the size and composition of the complexes but also the nature of the antigen within the complex can influence the clearance and organ localization of circulating immune complexes. 相似文献
10.
Restricted usage of VH and V kappa genes by murine monoclonal antibodies against 3-fucosyllactosamine 总被引:4,自引:0,他引:4
We are studying the structure and regulation of murine antibodies against the 3-fucosyllactosamine antigenic determinant. Analysis of the sequences of seven BALB/c IgM, kappa monoclonal antibodies (mAb), obtained from four fusions, indicates that these antibodies exhibit restriction in their usage of VH and VL genes. Based on a combination of mRNA sequences and Southern filter hybridization data, all seven light chains are encoded by V kappa 24B and J kappa 1 gene segments. Complete mRNA sequences of the heavy chains revealed that all seven mAb are encoded by VH441, six antibodies are encoded by JH4 and one uses a JH3 gene segment. The VH441 gene segment and all seven mAb contain a potential glycosylation site at Asn 58 in complementarity-determining region (CDR)2. In contrast to the similarity of the VH regions, the heavy chain CDR3 segments exhibit considerable heterogeneity. They are encoded by three D segments, they vary in length from 7-9 amino acids and display differences in their deduced amino acid sequences. The VH441 gene segment also encodes antibodies against four other carbohydrate antigens, levan, galactan, dextran and galactosyl globoside. The use of a single gene segment to encode antibodies against five different antigens suggests that the domain encoded by VH441 might be particularly well adapted for forming sites that bind carbohydrate determinants. Glycosylation of CDR2 might contribute to the unique properties of this VH domain. 相似文献