全文获取类型
收费全文 | 952篇 |
免费 | 107篇 |
专业分类
1059篇 |
出版年
2022年 | 9篇 |
2021年 | 22篇 |
2018年 | 7篇 |
2017年 | 7篇 |
2016年 | 7篇 |
2015年 | 21篇 |
2014年 | 50篇 |
2013年 | 48篇 |
2012年 | 68篇 |
2011年 | 67篇 |
2010年 | 36篇 |
2009年 | 28篇 |
2008年 | 38篇 |
2007年 | 45篇 |
2006年 | 45篇 |
2005年 | 48篇 |
2004年 | 40篇 |
2003年 | 31篇 |
2002年 | 40篇 |
2001年 | 48篇 |
2000年 | 25篇 |
1999年 | 27篇 |
1998年 | 13篇 |
1997年 | 9篇 |
1996年 | 7篇 |
1995年 | 10篇 |
1994年 | 10篇 |
1993年 | 8篇 |
1992年 | 15篇 |
1991年 | 7篇 |
1990年 | 8篇 |
1989年 | 19篇 |
1988年 | 5篇 |
1987年 | 9篇 |
1986年 | 15篇 |
1985年 | 9篇 |
1984年 | 15篇 |
1983年 | 12篇 |
1982年 | 6篇 |
1981年 | 12篇 |
1980年 | 7篇 |
1979年 | 5篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1975年 | 5篇 |
1974年 | 7篇 |
1911年 | 7篇 |
1909年 | 4篇 |
1908年 | 5篇 |
1906年 | 4篇 |
排序方式: 共有1059条查询结果,搜索用时 0 毫秒
1.
Four myeloid cell lines (M1, WEHI-3B D+, FDC-P1, and 32D) were screened for the presence of J11d antigen. One of these cell lines, the myeloid leukemia M1, was found to express a high level of J11d antigen on the cell surface. Recombinant mouse leukemic inhibitory factor (rm-LIF), recombinant human LIF (rh-LIF), and steroids (hydrocortisone and dexamethasone) could induce M1 cells to undergo monocytic differentiation. The level of J11d antigen was greatly reduced after treatment of the cells with LIF or steroids. Western blotting revealed that the apparent molecular weight of the J11d antigen on M1 cells was 45-48 kDa. Furthermore, the level of J11d mRNA was also reduced during LIF-induced differentiation of M1 cells. 相似文献
2.
Sensitization of mice with wild-type and cold-adapted influenza virus variants: immune response to two H1N1 and H3N2 viruses
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Two A strain influenza viruses, A/Hong Kong/123/77 (A/HK/123/77) (H1N1) and A/Queensland/6/72 (A/Qld/6/72) (H3N2), and the two cold-adapted reassortants which possess the surface antigens of these strains (CR35 and CR6, respectively) were tested for their ability both to induce primary cytotoxic T-cell (Tc cell) responses in mice and to sensitize mice for a second Tc cell response when challenged with a distantly related A strain virus, A/Shearwater/72 (H6N5). After intranasal inoculation, A/Qld/6/72 replicated to higher titers in the lung (1 to 2 log10 50% egg infective doses) than did A/HK/123/77 or either of the reassortants. A/Qld/6/72 induced higher Tc cell responses in the lung than did CR6, and both were more effective than either A/HK/123/77 or CR35 in this respect. When similar doses (10 or 10(3) hemagglutinin units) of each virus were injected intravenously into mice and the spleens were tested for Tc cell activity 6 days later, both A/Qld/6/72 and CR6 were ca. 100-fold better at inducing a primary Tc cell response than A/HK/123/77 or CR35. In contrast, the H1N1 and H3N2 viruses gave rather similar anti-hemagglutinin antibody titers (after intravenous injection) and delayed-type hypersensitivity reactions (after subcutaneous injection). If mice were primed with a low dose of these viruses (10(4) 50% egg infective doses intranasally), A/Qld/6/72 and CR6 were more effective than A/HK/123/77 or CR35 at sensitizing for a secondary Tc cell response when challenged with A/Shearwater/72, but if larger doses were given either intranasally (10(6) 50% egg infective doses) or intravenously (10 to 10(3) hemagglutinin units), all viruses sensitized the mice equally well, despite the fact the A/Shearwater/72 gives a poor primary Tc cell response in mice. Thus, the viral glycoprotein antigens can be important in determining the immunogenicity of the virus and, particularly, the class I antigen-restricted Tc cell response of the host. 相似文献
3.
The thermotropic phase behavior of a series of 1,2-diacylphosphatidylcholines containing linear saturated acyl chains of 10-22 carbons was studied by differential scanning calorimetry. When fully hydrated and thoroughly equilibrated by prolonged incubation at appropriate low temperatures, all of the compounds studied form an apparently stable subgel phase (the Lc phase). The formation of the stable Lc phase is a complex process which apparently proceeds via a number of metastable intermediates after being nucleated by incubation at appropriate low temperatures. The process of Lc phase formation is subject to considerable hysteresis, and our observations indicate that the kinetic limitations become more severe as the length of the acyl chain increases. The kinetics of Lc phase formation also depend upon whether the acyl chains contain an odd or an even number of carbon atoms. The Lc phase is unstable at higher temperatures and upon heating converts to the so-called liquid-crystalline state (the L alpha phase). The conversion from the stable Lc to the L alpha phase can be a direct, albeit a multistage process, as observed with very short chain phosphatidylcholines, or one or more stable gel states may exist between the Lc and L alpha states. For the longer chain compounds, conversions from one stable gel phase to another become separated on the temperature scale, so that discrete subtransition, pretransition, and gel/liquid-crystalline phase transition events are observed.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
4.
T cell tolerance to Mlsa encoded antigens in T cell receptor V beta 8.1 chain transgenic mice. 总被引:15,自引:3,他引:12
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
H Pircher T W Mak R Lang W Ballhausen E Rüedi H Hengartner R M Zinkernagel K Bürki 《The EMBO journal》1989,8(3):719-727
To study T cell tolerance, transgenic mice were generated that expressed the Mlsa-reactive T cell receptor (TCR) beta chain V beta 8.1 (cDNA) under the control of the H-2Kb promoter/immunoglobulin heavy chain enhancer on approximately 90% of peripheral T cells. In transgenic mice bearing Mlsa, thymocytes expressing the TCR at a high density were deleted and the percentage of Thy 1.2+ lymph node cells was reduced. The CD4/CD8 ratio of mature T cells was reversed in Mlsa and Mlsb transgenic mice independent of the H-2. RNA analysis and immunofluorescence with TCR V beta-specific antibodies revealed that expression of endogenous TCR beta genes was suppressed. Both Mlsa and Mlsb TCR beta chain transgenic mice mounted a T-cell-dependent IgG response against viral antigens, whereas the capacity to generate alloreactive and virus-specific cytotoxic T cells was impaired in TCR beta chain transgenic Mlsa, but not in transgenic Mlsb mice. 相似文献
5.
In our work evaluating the antioxidant properties of a number of cardiovascular drugs, we have emphasized the importance of lipophilicity as a property contributing to antioxidant potency. Thus, the dihydropyridine calcium channel blockers and propranolol, one of the most lipophilic beta-blockers, were found to exhibit the greatest potency in membrane and cellular models. Both beta-blockers and calcium channel blockers are classified as antihypertensive agents. We found that the specific chemical moieties of various drugs may participate in the antioxidant mechanism of action. While reviewing relevant work from the past literature, it became apparent that some of the chemical moieties of antihypertensive and vasodilator drugs may bind transition metals. Thus, this present review focuses on common properties of transition metal-interaction that are shared, to a greater or lesser degree, by a number of vasoactive drugs and chemical agents. Although this observation has been pursued by other investigators in the past, we submit that the potential relevance to the newer pharmacological agents needs to be explored further. In addition, new information regarding the role of transition metals and free radicals involving vascular cells focuses greater importance on transition metal-interaction as a potential mechanism in vasodilation. This review does not intend to be inclusive of all chemical structures capable of binding transition metals; only those that are clinically relevant will be considered in some detail. Potential mechanisms of metal-chelating actions leading to vasodilation are also discussed. 相似文献
6.
W P Fung-Leung M W Schilham A Rahemtulla T M Kündig M Vollenweider J Potter W van Ewijk T W Mak 《Cell》1991,65(3):443-449
A mutant mouse strain without CD8 (Lyt-2 and Lyt-3) expression on the cell surface has been generated by disrupting the Lyt-2 gene using embryonic stem cell technology. In these mice, CD8+ T lymphocytes are not present in peripheral lymphoid organs, but the CD4+ T lymphocyte population seems to be unaltered. Cytotoxic response of T lymphocytes from these mice against alloantigens and viral antigens is dramatically decreased. Proliferative response against alloantigens and in vivo help to B lymphocytes, however, are not affected. These data suggest that CD8 is necessary for the maturation and positive selection of class I MHC restricted cytotoxic T lymphocytes but is not required on any of the intermediate thymocyte populations (CD8+CD4-TcR- or CD4+CD8+TcRlow) during the development of functional class II MHC restricted helper T cells. 相似文献
7.
Unconfined compression of hydrated viscoelastic tissues: a biphasic poroviscoelastic analysis 总被引:2,自引:0,他引:2
A F Mak 《Biorheology》1986,23(4):371-383
A biphasic poroviscoelastic theory was used to analyze the unconfined compression creep and stress relaxation of a hydrated viscoelastic tissue. The intrinsic shear properties of the tissue matrix was described by an integral-type viscoelastic constitutive law while the intrinsic bulk property of the matrix was assumed to be linearly elastic. Parametric data were presented to show how the two major energy dissipative mechanisms, namely the interstitial fluid flow and the intrinsic matrix viscoelasticity, may each contribute to the apparent viscoelastic behavior of the whole tissue under unconfined compression. The hydraulic permeability of the tissue was found to enter in only as a scaling factor for time. 相似文献
8.
Comparison of the genomic sequences of the Friend spleen focus-forming virus with other murine retroviral sequences indicated that the spleen focus-forming virus was derived from at least three retroviruses. The 5' end of the virus, from the primer binding site through most of gag, was derived from AKV. The rest of gag and all of pol were of uncertain origin, but were probably derived from the same xenotropic virus that gave rise to the 5' half of env. The remainder was derived from Friend murine leukemia virus. The positions of a 585-base deletion, a 6-base duplication, and a point insertion that leads to a frame shift and premature protein termination in the ecotropic 3' end of env were invariant between three spleen focus-forming virus strains, indicating that they had a single common ancestor. However, the point of crossover between xenotropic viral sequences and Friend murine leukemia virus was different in each strain, and two strains were much more closely related to each other than to the third in the xenotropic region, indicating that these strains had diverged by multiple recombinations. Furthermore, a different nucleotide comprised the single point insertion near the 3' end of env, suggesting that these viruses have an extremely high transition and transversion rate. 相似文献
9.
Inhibition of protein synthesis enhances transformation of primary cells by viral DNA 总被引:2,自引:0,他引:2
Inhibition of protein synthesis by cycloheximide after transfection and subsequent removal of the drug increased the transformation efficiency of primary cells by plasmids containing the left 4.5, 6.7, or 16% of the adenovirus (Ad) genome. The enhancement factor ranged from 2 to as much as 70 depending on the size of the viral DNA fragments used. Addition of cycloheximide before or at the time of transfection inhibited transformation, suggesting that viral protein synthesis is important during the early phase of transformation. Transient expression assays showed that cells treated with cycloheximide post-transfection contained as much as three times the amount of viral RNA transcribed from regions E1A and E1B. Conversion of a rat cell line lacking thymidine kinase activity (TK-) to the TK+ phenotype by a plasmid containing the herpes TK gene was severely inhibited by the drug treatment, suggesting that the enhancement effects of cycloheximide on transformation may be specific for Ad DNA. Cycloheximide treatment also increased the number of transformants induced by a transformation defective E1B mutant of Ad12 (cyt mutant). Plasmid containing only the E1A region of Ad12 transformed primary rat kidney cells with very low efficiency. The inclusion of E1B in the transfecting DNA fragments increased the transformation frequency by more than 400-fold, much higher than that achieved by cycloheximide. Thus, cycloheximide cannot replace E1B functions in transformation efficiency. 相似文献
10.
Quantitation of serum immunoglobulin M, G, A, D and E levels was carried out in Malaysians with Brugia malayi infections. Results showed highly elevated levels of IgM and IgE as well as moderately elevated levels of IgG. These were most significant in patients with tropical pulmonary eosinophilia or elephantiasis. Serum IgE levels were extremely high in microfilaraemic patients (6,060 +/- 3,958 IU ml) probably due to a constant antigenic stimulation by dead and dying microfilariae. 相似文献