全文获取类型
收费全文 | 397篇 |
免费 | 18篇 |
国内免费 | 77篇 |
专业分类
儿科学 | 30篇 |
妇产科学 | 2篇 |
基础医学 | 30篇 |
口腔科学 | 6篇 |
临床医学 | 87篇 |
内科学 | 103篇 |
皮肤病学 | 16篇 |
神经病学 | 12篇 |
特种医学 | 93篇 |
外科学 | 16篇 |
综合类 | 24篇 |
预防医学 | 5篇 |
眼科学 | 6篇 |
药学 | 44篇 |
1篇 | |
中国医学 | 1篇 |
肿瘤学 | 16篇 |
出版年
2021年 | 3篇 |
2019年 | 2篇 |
2018年 | 2篇 |
2017年 | 4篇 |
2016年 | 4篇 |
2015年 | 10篇 |
2014年 | 10篇 |
2013年 | 8篇 |
2012年 | 3篇 |
2011年 | 10篇 |
2010年 | 5篇 |
2009年 | 16篇 |
2008年 | 7篇 |
2007年 | 57篇 |
2006年 | 8篇 |
2005年 | 19篇 |
2004年 | 3篇 |
2003年 | 6篇 |
2001年 | 7篇 |
2000年 | 12篇 |
1999年 | 8篇 |
1998年 | 22篇 |
1997年 | 31篇 |
1996年 | 26篇 |
1995年 | 22篇 |
1994年 | 18篇 |
1993年 | 14篇 |
1992年 | 4篇 |
1991年 | 7篇 |
1990年 | 9篇 |
1989年 | 10篇 |
1988年 | 14篇 |
1987年 | 6篇 |
1986年 | 10篇 |
1985年 | 12篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 13篇 |
1981年 | 12篇 |
1980年 | 9篇 |
1979年 | 3篇 |
1978年 | 6篇 |
1977年 | 5篇 |
1976年 | 8篇 |
1975年 | 8篇 |
1971年 | 2篇 |
1970年 | 1篇 |
1967年 | 1篇 |
1964年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有492条查询结果,搜索用时 15 毫秒
1.
2.
3.
Kundel HL; Gefter W; Aronchick J; Miller W Jr; Hatabu H; Whitfill CH; Miller W Sr 《Radiology》1997,205(3):859
4.
Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS 总被引:18,自引:0,他引:18
Storkebaum E Lambrechts D Dewerchin M Moreno-Murciano MP Appelmans S Oh H Van Damme P Rutten B Man WY De Mol M Wyns S Manka D Vermeulen K Van Den Bosch L Mertens N Schmitz C Robberecht W Conway EM Collen D Moons L Carmeliet P 《Nature neuroscience》2005,8(1):85-92
Neurotrophin treatment has so far failed to prolong the survival of individuals affected with amyotrophic lateral sclerosis (ALS), an incurable motoneuron degenerative disorder. Here we show that intracerebroventricular (i.c.v.) delivery of recombinant vascular endothelial growth factor (Vegf) in a SOD1(G93A) rat model of ALS delays onset of paralysis by 17 d, improves motor performance and prolongs survival by 22 d, representing the largest effects in animal models of ALS achieved by protein delivery. By protecting cervical motoneurons, i.c.v. delivery of Vegf is particularly effective in rats with the most severe form of ALS with forelimb onset. Vegf has direct neuroprotective effects on motoneurons in vivo, because neuronal expression of a transgene expressing the Vegf receptor prolongs the survival of SOD1(G93A) mice. On i.c.v. delivery, Vegf is anterogradely transported and preserves neuromuscular junctions in SOD1(G93A) rats. Our findings in preclinical rodent models of ALS may have implications for treatment of neurodegenerative disease in general. 相似文献
5.
CTLA-4 is required for the induction of high dose oral tolerance 总被引:5,自引:3,他引:5
Samoilova EB; Horton JL; Zhang H; Khoury SJ; Weiner HL; Chen Y 《International immunology》1998,10(4):491-498
Mucosal and systemic administrations of high dose antigens induce long-
lasting peripheral T cell tolerance. We and others have shown that high
dose peripheral T cell tolerance is mediated by anergy or deletion and is
preceded by T cell activation. Co-stimulatory molecules B7-1 (CD80)/B7-2
(CD86) and their counter-receptors CD28/CTLA-4 play pivotal roles in T cell
activation and immune regulation. In the present study, we examined the
roles of the B7 co-stimulation pathway in the generation of high dose
peripheral T cell tolerance. We found that blocking B7:CD28/CTLA-4
interaction at the time of tolerance induction partially prevented T cell
tolerance, whereas selective blockade of B7:CTLA-4 interaction completely
abrogated peripheral T cell tolerance induced by either oral or i.p.
antigens. These results suggest that CTLA-4-mediated feedback regulation
plays a crucial role in the induction of high dose peripheral T cell
tolerance.
相似文献
6.
Molecular genetic characterization of XRCC4 function 总被引:2,自引:0,他引:2
XRCC4 is a generally expressed protein of 334 amino acids that is involved
in the repair of DNA double-strand breaks and in V(D)J recombination, but
its function is unknown. In this study, we have used a mutational approach
and the yeast two-hybrid method to perform an initial characterization of
this protein. We show that the XRCC4 protein is located in the nucleus. We
also demonstrate that several potential phosphorylation sites are not
required for XRCC4 function in a transient V(D)J recombination assay. In
addition, we show that XRCC4 forms a homodimer in vivo with the
homodimerization domain being located within amino acids 115-204. Finally,
we define a core domain of XRCC4 that functions in V(D)J recombination and
comprises amino acids 18-204. Potential functions of XRCC4 are discussed.
相似文献
7.
Brites P Motley AM Gressens P Mooyer PA Ploegaert I Everts V Evrard P Carmeliet P Dewerchin M Schoonjans L Duran M Waterham HR Wanders RJ Baes M 《Human molecular genetics》2003,12(18):2255-2267
Rhizomelic chondrodysplasia punctata is a human autosomal recessive disorder characterized by skeletal, eye and brain abnormalities. The disorder is caused by mutations in the PEX7 gene, which encodes the receptor for a class of peroxisomal matrix enzymes. We describe the generation and characterization of a Pex7 mouse knockout (Pex7(-/-)). Pex7(-/-) mice are born severely hypotonic and have a growth impairment. Mortality in Pex7(-/-) mice is highest in the perinatal period although some Pex7(-/-) mice survived beyond 18 months. Biochemically Pex7(-/-) mice display the abnormalities related to a Pex7 deficiency, i.e. a severe depletion of plasmalogens, impaired alpha-oxidation of phytanic acid and impaired beta-oxidation of very-long-chain fatty acids. In the intermediate zone of the developing cerebral cortex Pex7(-/-) mice have an increase in neuronal density. In vivo neuronal birthdating revealed that Pex7(-/-) mice have a delay in neuronal migration. Analysis of bone ossification in newborn Pex7(-/-) mice revealed a defect in ossification of distal bone elements of the limbs as well as parts of the skull and vertebrae. These findings demonstrate that Pex7 knockout mice provide an important model to study the role of peroxisomal functioning in the pathogenesis of the human disorder. 相似文献
8.
Summary. Feline infectious peritonitis virus (FIPV) (Coronaviridae) causes the most lethal viral infection in cats: FIP. The related feline enteric coronavirus (FECV) causes mild enteritis.
Why these feline coronaviruses manifest so differently in vivo is not known. In this study, infection kinetics (titres and antigen expression) of FIPV 79-1146, and FECV 79-1683, were determined
in peripheral blood monocytes from 3 donor cats and compared to those in Crandell feline kidney (CrFK) cells. The infection
kinetics in monocytes were host dependent. Monocytes from 1 cat were resistant to both FIPV- and FECV-infection. Monocytes
from the other 2 cats could initially be infected by both FIPV and FECV but FIPV infection was sustained in monocytes of only
one cat. FECV-infection was never sustained and viral production was up to 100 times lower than in FIPV-infected monocytes.
In CrFK cells, FIPV and FECV infection kinetics did not differ. In monocytes of a larger cat population (n = 19) the 3 infection
patterns were also found. Considering all 22 investigated cats, 3/22 were not susceptible for FIPV and FECV. The rest could
be infected with FECV and FIPV but 10/22 cats had monocytes that only sustained FIPV infection and 9/22 sustained neither
FIPV nor FECV infection.
Both authors contributed equally. 相似文献
9.
Liu JQ; Bai XF; Shi FD; Xiao BG; Li HL; Levi M; Mustafa M; Wahren B; Link H 《International immunology》1998,10(8):1139-1148
Induction of mucosal tolerance by inhalation of soluble peptides with
defined T cell epitopes is receiving much attention as a means of
specifically down-regulating pathogenic T cell reactivities in autoimmune
and allergic disorders. Experimental autoimmune encephalomyelitis (EAE)
induced in the Lewis rat by immunization with myelin basic protein (MBP)
and Freund's adjuvant (CFA) is mediated by CD4+ T cells specific for the
MBP amino acid sequences 68-86 and 87-99. To further define the principles
of nasal tolerance induction, we generated three different MBP peptides
(MBP 68-86, 87-99 and the non- encephalitogenic peptide 110-128), and
evaluated whether their nasal administration on day -11, -10, -9, -8 and -7
prior to immunization with guinea pig MBP (gp-MBP) + CFA confers protection
to Lewis rat EAE. Protection was achieved with the encephalitogenic
peptides MBP 68-86 and 87-99, MBP 68-86 being more potent, but not with MBP
110-128. Neither MBP 68-86 nor 87-99 at doses used conferred complete
protection to gp-MBP-induced EAE. In contrast, nasal administration of a
mixture of MBP 68-86 and 87-99 completely blocked gp-MBP-induced EAE even
at lower dosage compared to that being used for individual peptides. Rats
tolerized with MBP 68-86 + 87-99 nasally showed decreased T cell responses
to MBP reflected by lymphocyte proliferation and IFN-gamma ELISPOT assays.
Rats tolerized with MBP 68-86 + 87-99 also had abrogated MBP-reactive
IFN-gamma and tumor necrosis factor-alpha mRNA expression in lymph node
cells compared to rats receiving MBP 110-128 nasally, while similar low
levels of MBP-reactive transforming growth factor-beta and IL-4 mRNA
expressing cells were observed in the two groups. Nasal administration of
MBP 68-86 + 87-99 only slightly inhibited guinea pig spinal cord
homogenate-induced EAE, and passive transfer of spleen mononuclear cells
from MBP 68-86 + 87-99-tolerized rats did not protect naive rats from EAE.
Finally, we show that nasal administration of MBP 68-86 + 87-99 can reverse
ongoing EAE induced with gp-MBP, although higher doses are required
compared to the dosage needed for prevention. In conclusion, nasal
administration of encephalitogenic MBP peptides can induce antigen-specific
T cell tolerance and confer incomplete protection to gp-MBP-induced EAE,
and MBP 68-86 and 87-99 have synergistic effects. Non-regulatory mechanisms
are proposed to be responsible for tolerance development after nasal
peptide administration.
相似文献
10.