全文获取类型
收费全文 | 140篇 |
免费 | 5篇 |
出版年
2020年 | 1篇 |
2019年 | 1篇 |
2017年 | 2篇 |
2016年 | 6篇 |
2015年 | 5篇 |
2014年 | 3篇 |
2013年 | 8篇 |
2012年 | 2篇 |
2011年 | 11篇 |
2010年 | 4篇 |
2009年 | 1篇 |
2008年 | 9篇 |
2007年 | 9篇 |
2006年 | 2篇 |
2005年 | 4篇 |
2004年 | 3篇 |
2003年 | 2篇 |
2002年 | 8篇 |
2001年 | 4篇 |
2000年 | 6篇 |
1999年 | 9篇 |
1998年 | 5篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
排序方式: 共有145条查询结果,搜索用时 31 毫秒
51.
The purpose of this paper is to review the economic and social implications of cloned cattle, their products, and their offspring as related to production agriculture. Cloning technology in cattle has several applications outside of traditional production agriculture. These applications can include bio-medical applications, such as the production of pharmaceuticals in the blood or milk of transgenic cattle. Cloning may also be useful in the production of research models. These models may or may not include genetic modifications. Uses in agriculture include many applications of the technology. These include making genetic copies of elite seed stock and prize winning show cattle. Other purposes may range from "insurance" to making copies of cattle that have sentimental value, similar to cloning of pets. Increased selection opportunities available with cloning may provide for improvement in genetic gain. The ultimate goal of cloning has often been envisioned as a system for producing quantity and uniformity of the perfect dairy cow. However, only if heritability were 100%, would clone mates have complete uniformity. Changes in the environment may have significant impact on the productivity and longevity of the resulting clones. Changes in consumer preferences and economic input costs may all change the definition of the perfect cow. The cost of producing such animals via cloning must be economically feasible to meet the intended applications. Present inefficiencies limit cloning opportunities to highly valued animals. Improvements are necessary to move the applications toward commercial application. Cloning has additional obstacles to conquer. Social and regulatory acceptance of cloning is paramount to its utilization in production agriculture. Regulatory acceptance will need to address the animal, its products, and its offspring. In summary, cloning is another tool in the animal biotechnology toolbox, which includes artificial insemination, sexing of semen, embryo sexing and in vitro fertilization. While it will not replace any of the above mentioned, its degree of utilization will depend on both improvement in efficiency as well as social and regulatory acceptance. 相似文献
52.
Porcine sperm factor supports activation and development of bovine nuclear transfer embryos 总被引:7,自引:0,他引:7
A study was undertaken to determine whether injection of porcine sperm factors (pSF), which trigger oscillations in intracellular calcium concentration ([Ca(2+)](i)) in mammalian oocytes, could be used to activate bovine oocytes during nuclear transfer. To date, only combined treatments that induce a monotonic rise in [Ca(2+)](i) and inhibit either phosphorylation or protein synthesis have been utilized in nuclear transfer. Several doses of pSF were tested. Injection of 5 mg/ml pSF triggered [Ca(2+)](i) oscillations that resembled those associated with fertilization with respect to amplitude and periodicity, and as a result, a high percentage of oocytes underwent activation. Furthermore, this concentration of pSF supported in vitro and in vivo development up to 60-90 days of gestation, comparable to development in control nuclear transfer embryos. Nevertheless, neither activation procedure supported development as well as did fertilization. The effectiveness of pSF as an activating agent in bovine oocytes may have been compromised because pSF was unable to support oscillations past 3-5 h postinjection and a second injection was necessary to extend the [Ca(2+)](i) oscillations. Likewise, a single injection of pSF failed to trigger downregulation of the inositol 1,4,5-trisphosphate receptor 1 subtype, whereas a second injection downregulated the receptor in a manner similar to that seen in fertilized oocytes. These results demonstrate that soluble factor(s) from porcine sperm can support early development in bovine nuclear transfer embryos; however, the efficacy may be limited because of the premature cessation of the induced oscillations. 相似文献
53.
Frederique M Moret Cornelis E Hack Kim MG van der Wurff-Jacobs Wilco de Jager Timothy RDJ Radstake Floris PJG Lafeber Joel AG van Roon 《Arthritis research & therapy》2013,15(5):R155
Introduction
Myeloid dendritic cells (mDCs) are potent T cell-activating antigen-presenting cells that have been suggested to play a crucial role in the regulation of immune responses in many disease states, including rheumatoid arthritis (RA). Despite this, studies that have reported on the capacity of naturally occurring circulating mDCs to regulate T cell activation in RA are still lacking. This study aimed to evaluate the phenotypic and functional properties of naturally occurring CD1c (BDCA-1)+ mDCs from synovial fluid (SF) compared to those from peripheral blood (PB) of RA patients.Methods
CD1c+ mDC numbers and expression of costimulatory molecules were assessed by fluorescence-activated cell sorting (FACS) analysis in SF and PB from RA patients. Ex vivo secretion of 45 inflammatory mediators by mDCs from SF and PB of RA patients was determined by multiplex immunoassay. The capacity of mDCs from SF to activate autologous CD4+ T cells was measured.Results
CD1c+ mDC numbers were significantly increased in SF versus PB of RA patients (mean 4.7% vs. 0.6%). mDCs from SF showed increased expression of antigen-presenting (human leukocyte antigen (HLA) class II, CD1c) and costimulatory molecules (CD80, CD86 and CD40). Numerous cytokines were equally abundantly produced by mDCs from both PB and SF (including IL-12, IL-23, IL-13, IL-21). SF mDCs secreted higher levels of interferon γ-inducible protein-10 (IP-10), monokine induced by interferon γ (MIG) and, thymus and activation-regulated chemokine (TARC), but lower macrophage-derived chemokine (MDC) levels compared to mDCs from PB. mDCs from SF displayed a strongly increased capacity to induce proliferation of CD4+ T cells associated with a strongly augmented IFNγ, IL-17, and IL-4 production.Conclusions
This study suggests that increased numbers of CD1c+ mDCs in SF are involved in the inflammatory cascade intra-articularly by the secretion of specific T cell-attracting chemokines and the activation of self-reactive T cells. 相似文献54.
E Taslidere N Vardi H Parlakpinar A Yıldız B Taslidere MG Karaaslan 《Biotechnic & histochemistry》2013,88(7):485-495
We evaluated the effects of melatonin on acetylsalicylic acid (ASA) induced gastroduodenal and jejunal mucosal injury. We used 40 postpubertal rats divided randomly into five groups of eight animals. The control group consisted of untreated animals. The Mel group was injected intraperitoneally (i.p.) with 5 mg/kg melatonin. The ASA group was injected i.p. with 200 mg/kg ASA. The ASA + Mel group was injected i.p. with 5 mg/kg melatonin 45 min after administering 200 mg/kg ASA i.p. The Mel + ASA group was injected i.p. with 5 mg/kg melatonin 45 min before administering 200 mg/kg ASA i.p. We found no statistically significant differences in mean histopathological scores in the ASA + Mel group compared to the ASA group. ASA caused shortened villi and loss of the apical villus in the duodenum. The histopathological score was increased and villus height was decreased in the ASA group compared to untreated controls. Treatment with melatonin attenuated the histological damage. In the ASA group, occasional areas showed erosion of villi in the jejunum; however, differences in mean histopathological score in ASA group compared to the other groups were not statistically significant. Malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activities were measured in stomach, duodenal and jejunum tissue. We found increased MDA activity in both stomach and duodenal tissues in the ASA group compared to the control group (p < 0.05). We found no statistically significant changes in MDA levels in jejunal tissue in the ASA group compared to the control group. We found no change in SOD activity in either stomach or duodenal tissues in the ASA group compared to the control group. We observed decreased SOD activity in jejunal tissue in the ASA group compared to the control group (p < 0.05). We detected no change in GSH activity in stomach, duodenal or jejunal tissues in the ASA group compared to the control group. The stomach damage was less in melatonin treated groups, but the lesions were not completely eliminated. The jejunum in the ASA group retained a nearly normal appearance. We found that melatonin exhibited some healing effects on ASA induced duodenal mucosal injury. 相似文献
55.
Ye XY Chen SY Nayeem A Golla R Seethala R Wang M Harper T Sleczka BG Li YX He B Kirby M Gordon DA Robl JA 《Bioorganic & medicinal chemistry letters》2011,21(22):6699-6704
Starting from high throughput screening hit 2-adamantyl acetic acid 3, a series of polycyclic acids have been designed and synthesized as novel, potent, and selective inhibitors of human 11β-HSD-1. Structure-activity relationships of two different regions of the chemotype (polycyclic ring and substituents on quaternary carbon) are discussed. 相似文献
56.
Wang H Robl JA Hamann LG Simpkins L Golla R Li YX Seethala R Zvyaga T Gordon DA Li JJ 《Bioorganic & medicinal chemistry letters》2011,21(14):4146-4149
A series of pyridyl amide/sulfonamide inhibitors of 11β-HSD-1 were modified to incorporate a novel 1,2,4-triazolopyridine scaffold. Optimization of substituents at the 3 and 8 position of the TZP core, with a special focus on enhancing metabolic stability, resulted in the identification of compound 38 as a potent and metabolically stable inhibitor of the enzyme. 相似文献
57.
Ngu K Weinstein DS Liu W Langevine C Combs DW Zhuang S Chen X Madsen CS Harper TW Ahmad S Robl JA 《Bioorganic & medicinal chemistry letters》2011,21(14):4141-4145
A series of inhibitors of mammalian 15-lipoxygenase (15-LO) based on a 3,4,5-tri-substituted pyrazole scaffold is described. Replacement of a sulfonamide functionality in the lead series with a sulfamide group resulted in improved physicochemical properties generating analogs with enhanced inhibition in cell-based and whole blood assays. 相似文献
58.
Simpkins LM Bolton S Pi Z Sutton JC Kwon C Zhao G Magnin DR Augeri DJ Gungor T Rotella DP Sun Z Liu Y Slusarchyk WS Marcinkeviciene J Robertson JG Wang A Robl JA Atwal KS Zahler RL Parker RA Kirby MS Hamann LG 《Bioorganic & medicinal chemistry letters》2007,17(23):6476-6480
The synthesis and structure-activity relationships of novel dipeptidyl peptidase IV inhibitors replacing the classical cyanopyrrolidine P1 group with other small nitrogen heterocycles are described. A unique potency enhancement was achieved with beta-branched natural and unnatural amino acids, particularly adamantylglycines, linked to a (2S,3R)-2,3-methanopyrrolidine based scaffold. 相似文献
59.
Ricardo Guerra Peixe Marcela Santana Bastos Boechat Alba Lucinia Peixoto Rangel Rh?nia Fran?a Gomes Rosa Maria Luiza Petzl-Erler Lilian MG Bahia-Oliveira 《Memórias do Instituto Oswaldo Cruz》2014,109(1):99-107
The association of single nucleotide polymorphisms (SNPs) in the interferon (IFN)-γ
gene ( IFNG ) with different types of retinal scar lesions
presumably caused by toxoplasmosis were investigated in a cross-sectional
population-based genetic study. Ten SNPs were investigated and after Bonferroni
correction, only the associations between SNPs rs2069718 and
rs3181035 with retinal/retinochoroidal scar lesions type A (most
severe scar lesions) and C (least severe scar lesions), respectively, remained
significant. The associations of two different IFNG SNPs with two
different types of retinal lesions attributable to toxoplasmosis support the
hypothesis that different inflammatory mechanisms underlie the development of these
lesions. The in vitro analysis of IFN-γ secretion by peripheral blood mononuclear
cells stimulated with Toxoplasma gondii antigens was also
investigated. The association between SNP rs2069718 and type A scar
lesions revealed that differential IFN-γ levels are correlated with distinct
genotypes. However, no correlation was observed with IFN-γ secretion levels and the
SNP rs3181035 , which was significantly associated with type C scar
lesions. Our findings strongly suggest that immunogenetic studies of individuals with
congenital or postnatally acquired infection are needed to better understand the role
of IFN-γ and its polymorphisms in the pathogenesis of ocular toxoplasmosis. 相似文献