全文获取类型
收费全文 | 1277篇 |
免费 | 175篇 |
专业分类
1452篇 |
出版年
2021年 | 11篇 |
2016年 | 13篇 |
2015年 | 38篇 |
2014年 | 32篇 |
2013年 | 61篇 |
2012年 | 56篇 |
2011年 | 58篇 |
2010年 | 35篇 |
2009年 | 35篇 |
2008年 | 40篇 |
2007年 | 50篇 |
2006年 | 60篇 |
2005年 | 64篇 |
2004年 | 52篇 |
2003年 | 59篇 |
2002年 | 50篇 |
2001年 | 30篇 |
2000年 | 55篇 |
1999年 | 42篇 |
1998年 | 15篇 |
1997年 | 16篇 |
1996年 | 15篇 |
1995年 | 10篇 |
1994年 | 14篇 |
1993年 | 13篇 |
1992年 | 30篇 |
1991年 | 33篇 |
1990年 | 30篇 |
1989年 | 33篇 |
1988年 | 19篇 |
1987年 | 33篇 |
1986年 | 28篇 |
1985年 | 23篇 |
1984年 | 29篇 |
1983年 | 15篇 |
1982年 | 10篇 |
1981年 | 14篇 |
1980年 | 22篇 |
1979年 | 13篇 |
1978年 | 14篇 |
1977年 | 18篇 |
1976年 | 19篇 |
1975年 | 12篇 |
1974年 | 18篇 |
1973年 | 11篇 |
1972年 | 16篇 |
1969年 | 10篇 |
1967年 | 8篇 |
1966年 | 10篇 |
1965年 | 9篇 |
排序方式: 共有1452条查询结果,搜索用时 0 毫秒
71.
Defective or inefficient apoptosis is an acquired hallmark of cancer cells. Thus, a thorough understanding of apoptotic signaling pathways and insights into apoptosis resistance mechanisms are imperative to unravel novel drug targets for the design of more effective and target selective therapeutic strategies. This review aims at providing an overview of the recent understanding of apoptotic signaling pathways, the main mechanisms by which cancer cells resist apoptotic insults, and discusses some recent attempts to target the mitochondrion for restoring efficient cell death signaling in cancer cells. 相似文献
72.
Permselectivity of the glomerular capillary wall to macromolecules. I. Theoretical considerations. 总被引:1,自引:0,他引:1 下载免费PDF全文
The transport of macromolecules across the renal glomerular capillary wall has been described theoretically using flux equations based on (a) restricted transport through small pores, and (b) the Kedem-Katchalsky formulation. The various assumptions and limitations inherent in these two approaches are discussed. To examine the coupling between macromolecular solute transport and the determinants of glomerular filtration rate, these flux equations were combined with mass balance relations which allow for variations in the transmembrane driving forces along a glomerular capillary. It was predicted, using both pore theory and the Kedem-Katchalsky equations, that fractional solute clearance should be strongly dependent on the determinants of glomerular filtration rate when convection and diffusion both contribute to solute transport. When convection becomes the sole mechanism for transcapillary solute transport, however, fractional solute clearance is essentially independent of changes in the determinants of glomerular filtration rate. Consequently, unless diffusion is absent, fractional solute clearances alone are insufficient to characterize the permselective properties of the glomerular capillary wall, since these values may be altered by changes in glomerular pressures and flows as well as changes in the properties of the capillary wall per se. 相似文献
73.
Lack of Nucleotide Sequence Relationship Among the Temperate Bacteriophage SPO2, Bacillus subtilis, and Virulent Bacteriophages β3 and β22 下载免费PDF全文
Radiolabeled phage SPO2 fragments were tested for the abiity to form interspecies deoxyribonucleic acid (DNA) duplexes with DNA from Bacillus subtilis and from phages beta3 and beta22. No reassociation, above control values, occurred between the DNA of phage SPO2 and that of its host or either of the virulent B. subtilis phages. It appears that extensive nucleotide sequence similarities between portions of host and phage DNA species are not necessary for the formation of the lysogenic state. The thermal elution profile of reassociated SPO2 DNA exhibited a normal distribution, indicating no heterogeneity in base composition. This differs from temperate enterophages whose DNA molecules contain regions of differing base composition. 相似文献
74.
Barral DC Cavallari M McCormick PJ Garg S Magee AI Bonifacino JS De Libero G Brenner MB 《Traffic (Copenhagen, Denmark)》2008,9(9):1446-1457
CD1 proteins are a family of major histocompatibility complex (MHC) class I-like antigen-presenting molecules that present lipids to T cells. The cytoplasmic tails (CTs) of all human CD1 isoforms, with the exception of CD1a, contain tyrosine-based sorting motifs, responsible for the internalization of proteins by the clathrin-mediated pathway. The role of the CD1a CT, which does not possess any sorting motifs, as well as its mode of internalization are not known. We investigated the internalization and recycling pathways followed by CD1a and the role of its CT. We found that CD1a can be internalized by a clathrin- and dynamin-independent pathway and that it follows a Rab22a- and ADP ribosylation factor (ARF)6-dependent recycling pathway, similar to other cargo internalized independent of clathrin. We also found that the CD1a CT is S-acylated. However, this posttranslational modification does not determine the rate of internalization or recycling of the protein or its localization to detergent-resistant membrane microdomains (DRMs) where we found CD1a to be enriched. We also show that plasma membrane DRMs are essential for efficient CD1a-mediated antigen presentation. These findings place CD1a closer to MHC class I in its trafficking and potential antigen-loading compartments among CD1 isoforms. Furthermore, we identify CD1a as a new marker for the clathrin- and dynamin-independent and DRM-dependent pathway of internalization as well as the Rab22a- and ARF6-dependent recycling pathway. 相似文献
75.
Summary The effect of three different carbon sources on the biosynthesis of polyunsaturated fatty acids of the-linolenic acid series was investigated in hepatoma tissue culture (HTC) cells. Alpha linolenic acid was converted to higher homologs by a desaturating route that synthetized mainly 18:4 (6, 9, 12, 15), 20:4 (8, 11, 14, 17) and 20:5 (5, 8, 11, 14, 17) and an elongating route that produced 20:3 (11, 14, 17) and 20:4 (5, 11, 14, 17) acids. Fasting decreased both biosynthetic routes whereas glucose reactivated only the elongating pathway. Lactalbumin hydrolysate enhanced significantly only the desaturating route whereas glycerol was inactive. Glucose and aminoacids increased similarly the incorporation of labeled linolenic acid in the cells. The results are independent of hormonal effects.Members of the Carrera del Investigador Científico of the Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina. 相似文献
76.
Two fuel utilizers, a strain of Pseudomonas aeruginosa and a Hormodendrum sp., and two fuel isolates which did not use fuel, Staphylococcus and Bacillus spp., were tested for ability to survive and grow in systems containing emulsified or nonemulsified forms of JP-4 jet fuel. Neither emulsion (Alamac no. 1 or Alamac no. 2) supported microbial growth without a water phase. Growth of P. aeruginosa in liquid systems containing either emulsion was not significantly different from growth in liquid systems with nonemulsified fuel. The Hormodendrum sp. grew well in a liquid medium containing nonemulsified JP-4, but when either of the emulsions served as carbon source no growth was observed. However, good growth was noted on spread plates with either emulsion. Viable cells of Bacillus sp. did not increase over a 4-day period, and Staphylococcus sp. did not survive in liquid systems containing JP-4 or emulsions. 相似文献
77.
Effect of Temperature and Salinity Stress on Growth and Lipid Composition of Shewanella gelidimarina 下载免费PDF全文
David S. Nichols June Olley Horacio Garda Rodolfo R. Brenner Tom A. McMeekin 《Applied microbiology》2000,66(6):2422-2429
The maximum growth temperature, the optimal growth temperature, and the estimated normal physiological range for growth of Shewanella gelidimarina are functions of water activity (aw), which can be manipulated by changing the concentration of sodium chloride. The growth temperatures at the boundaries of the normal physiological range for growth were characterized by increased variability in fatty acid composition. Under hyper- and hypoosmotic stress conditions at an aw of 0.993 (1.0% [wt/vol] NaCl) and at an aw of 0.977 (4.0% [wt/vol] NaCl) the proportion of certain fatty acids (monounsaturated and branched-chain fatty acids) was highly regulated and was inversely related to the growth rate over the entire temperature range. The physical states of lipids extracted from samples grown at stressful aw values at the boundaries of the normal physiological range exhibited no abrupt gel-liquid phase transitions when the lipids were analyzed as liposomes. Lipid packing and adaptational fatty acid composition responses are clearly influenced by differences in the temperature-salinity regime, which are reflected in overall cell function characteristics, such as the growth rate and the normal physiological range for growth. 相似文献
78.
Mitochondrial membrane permeabilization by HIV-1 Vpr 总被引:1,自引:0,他引:1
The mitochondrion is a privileged target for apoptosis-modulatory proteins of viral origin. Thus, viral protein R (Vpr) can target mitochondria and induce apoptosis via a specific interaction with the permeability transition pore complex (PTPC). Vpr cooperates with the adenine nucleotide translocator (ANT) to form large conductance channels and to trigger all the hallmarks of mitochondrial membrane permeabilization (MMP). The Vpr/ANT interaction is direct, since it is abolished by the addition of a peptide corresponding to the Vpr binding site of ANT, ADP, ATP, or by Bcl-2. Accordingly, Vpr modulates MMP through direct structural and functional interactions with PTPC proteins. 相似文献
79.
IFN-gamma and IL-10 mediate parasite-specific immune responses of cord blood cells induced by pregnancy-associated Plasmodium falciparum malaria 总被引:4,自引:0,他引:4
Brustoski K Möller U Kramer M Petelski A Brenner S Palmer DR Bongartz M Kremsner PG Luty AJ Krzych U 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(3):1738-1745
Available evidence suggests that immune cells from neonates born to mothers with placental Plasmodium falciparum (Pf) infection are sensitized to parasite Ag in utero but have reduced ability to generate protective Th1 responses. In this study, we detected Pf Ag-specific IFN-gamma(+) T cells in cord blood from human neonates whose mothers had received treatment for malaria or who had active placental Pf infection at delivery, with responses being significantly reduced in the latter group. Active placental malaria at delivery was also associated with reduced expression of monocyte MHC class I and II in vivo and following short term in vitro coculture with Pf Ag compared with levels seen in neonates whose mothers had received treatment during pregnancy. Given that APC activation and Th1 responses are driven in part by IFN-gamma and down-regulated by IL-10, we examined the role of these cytokines in modulating the Pf Ag-specific immune responses in cord blood samples. Exogenous recombinant human IFN-gamma and neutralizing anti-human IL-10 enhanced T cell IFN-gamma production, whereas recombinant human IFN-gamma also restored MHC class I and II expression on monocytes from cord blood mononuclear cells cocultured with Pf Ag. Accordingly, active placental malaria at delivery was associated with increased frequencies of Pf Ag-specific IL-10(+)CD4(+) T cells in cord blood mononuclear cell cultures from these neonates. Generation and maintenance of IL-10(+) T cells in utero may thus contribute to suppression of APC function and Pf Ag-induced Th1 responses in newborns born to mothers with placental malaria at delivery, which may increase susceptibility to infection later in life. 相似文献
80.
The complex of tropomyosin and troponin binds to actin and inhibits activation of myosin ATPase activity and force production of striated muscles at low free Ca(2+) concentrations. Ca(2+) stimulates ATP activity, and at subsaturating actin concentrations, the binding of NEM-modified S1 to actin-tropomyosin-troponin increases the rate of ATP hydrolysis even further. We show here that the Delta14 mutation of troponin T, associated with familial hypertrophic cardiomyopathy, results in an increase in ATPase rate like that seen with wild-type troponin in the presence of NEM-S1. The enhanced ATPase activity was not due to a decreased incorporation of mutant troponin T with troponin I and troponin C to form an active troponin complex. The activating effect was more prominent with a hybrid troponin (skeletal TnI, TnC, and cardiac TnT) than with all cardiac troponin. Thus it appears that changes in the troponin-troponin contacts that result from mutations or from forming hybrids stabilize a more active state of regulated actin. An analysis of the effect of the Delta14 mutation on the equilibrium binding of S1-ADP to actin was consistent with stabilization of an active state of actin. This change in activation may be important in the development of cardiac disease. 相似文献