全文获取类型
收费全文 | 885篇 |
免费 | 98篇 |
国内免费 | 9篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 54篇 |
妇产科学 | 9篇 |
基础医学 | 165篇 |
口腔科学 | 16篇 |
临床医学 | 71篇 |
内科学 | 281篇 |
皮肤病学 | 11篇 |
神经病学 | 47篇 |
特种医学 | 74篇 |
外科学 | 86篇 |
综合类 | 6篇 |
预防医学 | 55篇 |
眼科学 | 22篇 |
药学 | 30篇 |
肿瘤学 | 64篇 |
出版年
2023年 | 2篇 |
2022年 | 8篇 |
2021年 | 20篇 |
2020年 | 11篇 |
2019年 | 15篇 |
2018年 | 24篇 |
2017年 | 14篇 |
2016年 | 20篇 |
2015年 | 22篇 |
2014年 | 29篇 |
2013年 | 31篇 |
2012年 | 47篇 |
2011年 | 40篇 |
2010年 | 24篇 |
2009年 | 27篇 |
2008年 | 32篇 |
2007年 | 43篇 |
2006年 | 36篇 |
2005年 | 55篇 |
2004年 | 37篇 |
2003年 | 34篇 |
2002年 | 38篇 |
2001年 | 27篇 |
2000年 | 37篇 |
1999年 | 22篇 |
1998年 | 24篇 |
1997年 | 24篇 |
1996年 | 22篇 |
1995年 | 19篇 |
1994年 | 18篇 |
1993年 | 23篇 |
1992年 | 10篇 |
1991年 | 15篇 |
1990年 | 15篇 |
1989年 | 20篇 |
1988年 | 12篇 |
1987年 | 10篇 |
1986年 | 9篇 |
1985年 | 15篇 |
1984年 | 9篇 |
1983年 | 6篇 |
1982年 | 7篇 |
1981年 | 11篇 |
1980年 | 6篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1977年 | 7篇 |
1972年 | 3篇 |
1970年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有992条查询结果,搜索用时 31 毫秒
1.
2.
O'Brien SG Guilhot F Larson RA Gathmann I Baccarani M Cervantes F Cornelissen JJ Fischer T Hochhaus A Hughes T Lechner K Nielsen JL Rousselot P Reiffers J Saglio G Shepherd J Simonsson B Gratwohl A Goldman JM Kantarjian H Taylor K Verhoef G Bolton AE Capdeville R Druker BJ;IRIS Investigators 《The New England journal of medicine》2003,348(11):994-1004
3.
Laukkanen T Carr JK Janssens W Liitsola K Gotte D McCutchan FE Op de Coul E Cornelissen M Heyndrickx L van der Groen G Salminen MO 《Virology》2000,269(1):95-104
For reliable classification of HIV-1 strains appropriate reference sequences are needed. The HIV-1 genetic subtype F has a wide geographic spread, causing significant epidemics in South America, Africa, and some regions of Europe. Previously only two full-length sequences of each of the HIV-1 subtype F subclusters F1 and F2 have been described. To extend the knowledge of subtype F variation on a complete genome level, three new virtually full-length F1 sequences were cloned and sequenced, two from Africa and one from South America. Comparison of the new and previously described sequences showed that monophyletic clustering of the subcluster F1 of subtype F is consistent and highly supported in all genome regions. Two additional full-length strains were shown to be mosaics of subtypes F and D. These epidemiologically unrelated F/D sequences showed similar chimeric structure, suggesting that they may represent a previously undescribed circulating recombinant form (CRF). This was supported by partial sequences from three additional unlinked F/D recombinants. Genetic distances in the phylogenetic trees suggest that the recombination event leading to the putative CRF occurred relatively long ago, close to the divergence of the F1 and F2 subclusters. Furthermore, all five F/D recombinants are linked to the Democratic Republic of Congo, suggesting that the original recombination event took place in central Africa. 相似文献
4.
5.
Polstra AM Van Den Burg R Goudsmit J Cornelissen M 《Journal of clinical microbiology》2003,41(12):5488-5491
Human herpesvirus 8 (HHV-8) (or Kaposi's sarcoma [KS]-associated herpesvirus) is associated with all forms of KS. HHV-8 DNA load in peripheral blood mononuclear cells (PBMCs) of KS patients has been shown to correlate with the clinical stage of the disease. Studies have been done to assess the HHV-8 viral load in different sample types from KS patients and its clinical relevance. This paper describes the design and evaluation of a quantitative real-time (TaqMan) PCR assay for routine diagnosis of HHV-8 infection. The linear dynamic range was 5 to 5 x 10(6) copies of HHV-8 DNA (r(2) > 0.99). The assay is very sensitive, specific, and easily reproducible (less than 2% variability) and can be used for different clinical samples, such as serum, plasma, and PBMCs. The question of which clinical sample, serum or plasma, is preferable for HHV8 DNA testing was addressed, using this newly developed real-time PCR assay. From 85 patients with diagnosed AIDS-KS, matched plasma and serum samples were collected. Of the 85 patients tested, 35 were positive for HHV-8 DNA in both plasma and serum (41%), 8 were positive in serum but not plasma, and 7 had detectable HHV-8 DNA only in plasma. The HHV-8 load was similar in both plasma and serum, and no significant difference was found. However, more inhibition was seen in the plasma samples with the use of a system quality control, seal herpesvirus type 1. Therefore, our results suggest that serum is the preferred material for HHV-8 load testing, since there is less possible hindrance in the amplification than with plasma. 相似文献
6.
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
7.
Paradoxical effects of interleukin-10 on the maturation of murine myeloid dendritic cells 总被引:16,自引:0,他引:16
Commeren DL Van Soest PL Karimi K Löwenberg B Cornelissen JJ Braakman E 《Immunology》2003,110(2):188-196
The immunoregulatory cytokine, interleukin-10 (IL-10), has been shown to inhibit the maturation of human myeloid dendritic cells (DC). In the present study, we demonstrate that IL-10 has paradoxical effects on the maturation of murine myeloid bone marrow-derived DC. On the one hand, IL-10 inhibits the maturation of murine myeloid DC. The addition of IL-10 to granulocyte-macrophage colony-stimulating factor (GM-CSF)-supported murine BM-derived DC cultures reduced the frequency of major histocompatibility complex (MHC) class IIbright cells. These IL-10-pretreated DC have a reduced capacity to stimulate T cells in an allogeneic mixed leucocyte reaction. On the other hand, however, and in contrast to the effects of IL-10 on human DC, we found that the addition of IL-10 from the initiation of the culture onwards induced an up-regulation of the expression of the costimulatory molecules CD40, CD80 and CD86 on murine myeloid DC, as compared to DC generated with GM-CSF only. Moreover, a subpopulation of IL-10-pretreated MHC class IIdim DC lacked the capacity to take up dextran-fluorescein isothiocyanate (FITC), a feature of DC maturation. Taken together, our data demonstrate that the generation of murine myeloid DC in the presence of IL-10 results in a population of incompletely matured MHC class IIdim CD80+ CD86+ DC. These DC lack T-cell stimulatory capacity, suggesting a role for IL-10 in conferring tolerogenic properties on murine myeloid DC. 相似文献
8.
Hydrosalpinges adversely affect markers of endometrial receptivity 总被引:22,自引:10,他引:22
Meyer WR; Castelbaum AJ; Somkuti S; Sagoskin AW; Doyle M; Harris JE; Lessey BA 《Human reproduction (Oxford, England)》1997,12(7):1393-1398
While in-vitro fertilization (IVF) was initially developed in women with
tubal factor infertility, recent clinical studies have suggested that the
presence of hydrosalpinges lowers implantation and pregnancy rates. We
postulated that these hydrosalpinges cause impaired endometrial
receptivity. A total of 103 women with hydrosalpinges were prospectively
evaluated, and compared with 55 infertile and 44 fertile controls. All
women had endometrial biopsies during the window of implantation, analysed
by conventional histological criteria, and also stained for three integrin
markers of endometrial receptivity (alpha1beta1, alpha4beta1 and alpha
vbeta3). Women with hydrosalpinges (cases) expressed significantly less of
the alpha vbeta3 integrin compared with controls. There was no difference
in expression of alpha1beta1 or alpha4beta1 among groups. A significantly
greater number of cases had out of phase histology and missing alpha vbeta3
(type I defects) and absent integrin expression despite normal histological
maturation (type II) defects, compared with controls. Of 20 women with
impaired endometrial receptivity who were also biopsied after hydrosalpinx
surgery, 70% demonstrated increased alpha vbeta3 expression. Seventy-seven
percent of type I and 57% of type II defects were corrected
postoperatively. Using markers of endometrial receptivity, this study
demonstrates that inflammatory hydrosalpinges have an adverse effect on
endometrial receptivity, which in some cases may be overcome by surgical
treatment of the hydrosalpinx.
相似文献
9.
bcl-2 transgene expression promotes survival and reduces proliferation of CD3-CD4-CD8- T cell progenitors 总被引:16,自引:0,他引:16
Proliferative expansion and apoptotic cell death play prominent roles in T
cell development. The molecular control of cell cycle progression and
apoptosis appear to be inter-connected since the Bcl-2 protein can inhibit
apoptosis and slow cell cycle progression in cortical thymocytes and mature
T cells, particularly during the transition from the quiescent state into
the cell cycle. Here the impact of bcl-2 transgene expression on
CD3-CD4-CD8- T cell progenitors was assessed. Bcl-2 enhanced the survival
of these progenitors at all of the four major differentiation stages, CD25-
CD44+ (pro-T1), CD25 + CD44+ (pro- T2), CD25 + CD44- (pro-T3) and
CD25-CD44- (pro-T4). However, it reduced cell cycling and slowed turnover
only in the pro-T4 subset. From an analysis of bcl-2 transgenic mice
expressing a TCR transgene or bearing a mutation in the scid or rag-1 gene
we conclude that Bcl-2 inhibits proliferation only of T cell progenitors
that are activated via the pre- TCR, not those stimulated via c-Kit and the
IL-7 receptor.
相似文献
10.
Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism 总被引:3,自引:0,他引:3
Baron J; Winer KK; Yanovski JA; Cunningham AW; Laue L; Zimmerman D; Cutler GB Jr 《Human molecular genetics》1996,5(5):601-606
Parathyroid hormone secretion is negatively regulated by a 7- transmembrane
domain, G-protein coupled Ca(2+)-sensing receptor. We hypothesized that
activating mutations in this receptor might cause autosomal dominant
hypoparathyroidism (ADHP). Consistent with this hypothesis, we identified,
in two families with ADHP, heterozygous missense mutations in the
Ca(2+)-sensing receptor gene that cosegregated with the disorder. None of
50 normal controls had either mutation. We also identified a de novo,
missense Ca(2+)-sensing receptor mutation in a child with severe sporadic
hypoparathyroidism. The amino acid substitution in one ADHP family affected
the N-terminal, extracellular domain of the receptor. The other mutations
involved the transmembrane region. Unlike patients with acquired
hypoparathyroidism, patients with these mutations had hypercalciuria even
at low serum calcium concentrations. Their greater hypercalciuria
presumably reflected activation of Ca(2+)-sensing receptors in kidney
cells, where the receptor negatively regulates calcium reabsorption. This
augmented hypercalciuria increases the risk of renal complications and thus
has implications for the choice of therapy.
相似文献