全文获取类型
收费全文 | 3523篇 |
免费 | 409篇 |
出版年
2022年 | 15篇 |
2021年 | 56篇 |
2020年 | 30篇 |
2019年 | 48篇 |
2018年 | 56篇 |
2017年 | 50篇 |
2016年 | 76篇 |
2015年 | 126篇 |
2014年 | 147篇 |
2013年 | 199篇 |
2012年 | 259篇 |
2011年 | 260篇 |
2010年 | 157篇 |
2009年 | 123篇 |
2008年 | 241篇 |
2007年 | 256篇 |
2006年 | 217篇 |
2005年 | 204篇 |
2004年 | 192篇 |
2003年 | 169篇 |
2002年 | 172篇 |
2001年 | 51篇 |
2000年 | 46篇 |
1999年 | 51篇 |
1998年 | 56篇 |
1997年 | 32篇 |
1996年 | 40篇 |
1995年 | 37篇 |
1994年 | 29篇 |
1993年 | 38篇 |
1992年 | 34篇 |
1991年 | 36篇 |
1990年 | 30篇 |
1989年 | 24篇 |
1988年 | 17篇 |
1987年 | 17篇 |
1986年 | 13篇 |
1985年 | 20篇 |
1984年 | 21篇 |
1983年 | 22篇 |
1982年 | 20篇 |
1981年 | 14篇 |
1980年 | 19篇 |
1979年 | 15篇 |
1978年 | 19篇 |
1977年 | 19篇 |
1976年 | 13篇 |
1974年 | 12篇 |
1973年 | 20篇 |
1969年 | 16篇 |
排序方式: 共有3932条查询结果,搜索用时 46 毫秒
1.
2.
R. M. Davydov Joanne Smieja S. A. Dikanov Y. Zang Lawrence Que Jr. M. K. Bowman 《Journal of biological inorganic chemistry》1999,4(3):292-301
Radiolytic reduction at 77 K of oxo-/hydroxo-bridged dinuclear iron(III) complexes in frozen solutions forms kinetically
stabilized, mixed-valent species in high yields that model the mixed-valent sites of non-heme, diiron proteins. The mixed-valent
species trapped at 77 K retain ligation geometry similar to the initial diferric clusters. The shapes of the mixed-valent
EPR signals depend strongly on the bridging ligands. Spectra of the Fe(II)OFe(III) species reveal an S=1/2 ground state with small g-anisotropy as characterized by the uniaxial component (g
z
–g
av /2<0.03) observable at temperatures as high as ∼100 K. In contrast, hydroxo-bridged mixed-valent species are characterized
by large g-anisotropy (g
z
–g
av /2>0.03) and are observable only below 30 K. Annealing at higher temperatures causes structural relaxation and changes in
the EPR characteristics. EPR spectral properties allow the oxo- and hydroxo-bridged, mixed-valent diiron centers to be distinguished
from each other and can help characterize the structure of mixed-valent centers in proteins.
Received: 27 June 1998 / Accepted: 25 February 1999 相似文献
3.
4.
5.
Joanne K. Gardner Cyril D. S. Mamotte Priya Patel Teong Ling Yeoh Connie Jackaman Delia J. Nelson 《PloS one》2015,10(4)
Dendritic cells (DCs) play an important role in the generation of anti-cancer immune responses, however there is evidence that DCs in cancer patients are dysfunctional. Lipid accumulation driven by tumor-derived factors has recently been shown to contribute to DC dysfunction in several human cancers, but has not yet been examined in mesothelioma. This study investigated if mesothelioma tumor cells and/or their secreted factors promote increases in DC lipid content and modulate DC function. Human monocyte-derived DCs (MoDCs) were exposed to human mesothelioma tumor cells and tumor-derived factors in the presence or absence of lipoproteins. The data showed that immature MoDCs exposed to mesothelioma cells or factors contained increased lipid levels relative to control DCs. Lipid accumulation was associated with reduced antigen processing ability (measured using a DQ OVA assay), upregulation of the co-stimulatory molecule, CD86, and production of the tolerogenic cytokine, IL-10. Increases in DC lipid content were further enhanced by co-exposure to mesothelioma-derived factors and triglyceride-rich lipoproteins, but not low-density lipoproteins. In vivo studies using a murine mesothelioma model showed that the lipid content of tumor-infiltrating CD4+CD8α- DCs, CD4-CD8α- DCs DCs and plasmacytoid DCs increased with tumor progression. Moreover, increasing tumor burden was associated with reduced proliferation of tumor-antigen-specific CD8+ T cells in tumor-draining lymph nodes. This study shows that mesothelioma promotes DC lipid acquisition, which is associated with altered activation status and reduced capacity to process and present antigens, which may impair the ability of DCs to generate effective anti mesothelioma T cell responses. 相似文献
6.
Márcia M. Medeiros Henrique B. da Silva Aramys S. Reis Renato Barboza Joanne Thompson Maria Regina D'Império Lima Cláudio R. F. Marinho Carlos E. Tadokoro 《PloS one》2013,8(11)
It is postulated that accumulation of malaria-infected Red Blood Cells (iRBCs) in the liver could be a parasitic escape mechanism against full destruction by the host immune system. Therefore, we evaluated the in vivo mechanism of this accumulation and its potential immunological consequences. A massive liver accumulation of P. c. chabaudi AS-iRBCs (Pc-iRBCs) was observed by intravital microscopy along with an over expression of ICAM-1 on day 7 of the infection, as measured by qRT-PCR. Phenotypic changes were also observed in regulatory T cells (Tregs) and dendritic cells (DCs) that were isolated from infected livers, which indicate a functional role for Tregs in the regulation of the liver inflammatory immune response. In fact, the suppressive function of liver-Tregs was in vitro tested, which demonstrated the capacity of these cells to suppress naive T cell activation to the same extent as that observed for spleen-Tregs. On the other hand, it is already known that CD4+ T cells isolated from spleens of protozoan parasite-infected mice are refractory to proliferate in vivo. In our experiments, we observed a similar lack of in vitro proliferative capacity in liver CD4+ T cells that were isolated on day 7 of infection. It is also known that nitric oxide and IL-10 are partially involved in acute phase immunosuppression; we found high expression levels of IL-10 and iNOS mRNA in day 7-infected livers, which indicates a possible role for these molecules in the observed immune suppression. Taken together, these results indicate that malaria parasite accumulation within the liver could be an escape mechanism to avoid sterile immunity sponsored by a tolerogenic environment. 相似文献
7.
Childhood obesity is becoming a topic of great concern due to the rising prevalence of this condition in North America. Studies conducted in the United States have indicated that the prevalence of obesity has increased dramatically over the past few decades. The purpose of this study was to estimate the prevalence of obesity in Canadian children between the ages of 5 and 12 years by examining data from two national and two regional surveys. The 85th percentiles of each of four anthropometric indices derived from large normative populations were used as diagnostic criteria for obesity. As expected, the resulting prevalences varied according to the criteria used. A significant increase in childhood obesity between the 1981 to 1988 national surveys was observed when the three indices which used skinfolds were applied. Weight-for-height percentiles did not indicate an increase in obesity in these samples. Regional samples showed a less than expected prevalence of obesity among the middle-class children and a higher than expected rate among the inner city boys. It can be concluded that there is a need for a defined criteria for identifying obesity in children in order to avoid confusion resulting from the wide variation in estimates of prevalence resulting from different standards and measurements. Using adiposity-based criteria for obesity it was clearly evident that the prevalence of obesity has increased in Canadian children. 相似文献
8.
Calcium regulates inositol 1,3,4,5-tetrakisphosphate production in lysed thymocytes and in intact cells stimulated with concanavalin A. 总被引:2,自引:0,他引:2 下载免费PDF全文
Lysed mouse thymocytes release [3H]inositol 1,4,5 trisphosphate from [3H]inositol-labelled phosphatidyl inositol 4,5-bisphosphate in response to GTP gamma S, and rapidly phosphorylate [3H]inositol 1,4,5-trisphosphate to [3H]inositol 1,3,4,5-tetrakisphosphate. The rate of phosphorylation is increased approximately 7-fold when the free [Ca2+] in the lysate is increased from 0.1 to 1 microM, the range in which the cytosolic free [Ca2+] increases in intact thymocytes in response to the mitogen concanavalin A. Stimulation of the intact cells with concanavalin A also results in a rapid and sustained increase in the amount of inositol 1,3,4,5-tetrakisphosphate, and a much smaller transient increase in 1,4,5-trisphosphate. Lowering [Ca2+] in the medium from 0.4 mM to 0.1 microM before addition of concanavalin A reduces accumulation of inositol 1,3,4,5-tetrakisphosphate by at least 3-fold whereas the increase in inositol 1,4,5-trisphosphate is sustained rather than transient. The data imply that in normal medium the activity of the inositol 1,4,5-trisphosphate kinase increases substantially in response to the rise in cytosolic free [Ca2+] generated by concanavalin A, accounting for both the transient accumulation of inositol 1,4,5-trisphosphate and the sustained high levels of inositol 1,3,4,5-tetrakisphosphate. Inositol 1,3,4,5-tetrakisphosphate is a strong candidate for the second messenger for Ca2+ entry across the plasma membrane. This would imply that the inositol polyphosphates regulate both Ca2+ entry and intracellular Ca2+ release, with feedback control of the inositol polyphosphate levels by Ca2+. 相似文献
9.
10.
Cultures of dissociated brain cells from 15-day-old fetal mice were grown in the presence and absence of 20 or 50 nM triiodothyronine (T3), 30 or 300 nM cortisol, and 30 nM cortisol plus 50 nM T3 added to chemically defined media or in media supplemented with 15% serum from control and hypothyroid calves. The specific activities of five lysosomal enzymes--N-acetyl galactosaminidase, beta-glucuronidase, beta-galactosidase, cathepsin B, and dipeptidyl aminopeptidase I (DAP-I)--were higher in cells grown in calf serum than in cells grown in defined media. Of these enzymes, only DAP-I was elevated in activity when the cells were grown in hypothyroid calf serum instead of control calf serum. Elevation of DAP-I activity was reversed by addition of 20 nM T3 to hypothyroid calf serum. The enzymatic properties of DAP-I were similar whether the cells were grown in control or hypothyroid calf serum and were similar to those reported for human fibroblasts and the purified enzyme. When the cells were grown in defined media, cortisol decreased the activities of all lysosomal enzymes, with 300 nM cortisol being more effective than 30 nM cortisol. Addition of 50 nM T3 to 30 nM cortisol decreased DAP-I activity more than 30 nM cortisol alone, but 50 nM T3 alone in defined media did not alter DAP-I levels. The reduction of DAP-I activity in these cells by T3 required cortisol, unidentified components in serum, or both.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献