全文获取类型
收费全文 | 848篇 |
免费 | 96篇 |
出版年
2022年 | 8篇 |
2021年 | 11篇 |
2019年 | 9篇 |
2017年 | 11篇 |
2016年 | 18篇 |
2015年 | 35篇 |
2014年 | 34篇 |
2013年 | 41篇 |
2012年 | 54篇 |
2011年 | 45篇 |
2010年 | 32篇 |
2009年 | 26篇 |
2008年 | 29篇 |
2007年 | 41篇 |
2006年 | 28篇 |
2005年 | 34篇 |
2004年 | 34篇 |
2003年 | 37篇 |
2002年 | 21篇 |
2001年 | 25篇 |
2000年 | 26篇 |
1999年 | 22篇 |
1998年 | 8篇 |
1997年 | 12篇 |
1996年 | 10篇 |
1995年 | 7篇 |
1994年 | 10篇 |
1992年 | 11篇 |
1991年 | 20篇 |
1990年 | 18篇 |
1989年 | 17篇 |
1988年 | 12篇 |
1987年 | 14篇 |
1986年 | 9篇 |
1985年 | 10篇 |
1984年 | 8篇 |
1983年 | 9篇 |
1982年 | 4篇 |
1980年 | 7篇 |
1979年 | 9篇 |
1978年 | 12篇 |
1977年 | 14篇 |
1976年 | 7篇 |
1975年 | 12篇 |
1974年 | 6篇 |
1973年 | 13篇 |
1972年 | 10篇 |
1970年 | 7篇 |
1968年 | 5篇 |
1967年 | 5篇 |
排序方式: 共有944条查询结果,搜索用时 203 毫秒
121.
Many tissues express multiple gap junction proteins, or connexins (Cx); for example, Cx43, Cx40, and Cx37 are coexpressed in vascular cells. This study was undertaken to elucidate the consequences of coexpression of Cx40 or Cx37 with Cx43 at different ratios. EcR-293 cells (which endogenously produce Cx43) were transfected with ecdysone-inducible plasmids encoding Cx37 or Cx40. Immmunoblotting showed a ponasterone dose-dependent induction of Cx37 or Cx40 while constant levels of Cx43 were maintained. The coexpressed connexins colocalized at appositional membranes. Double whole-cell patch clamp recordings showed no significant change in total junctional conductances in cells treated with 0, 0.5, or 4?μM ponasterone; however, they did show a diversity of unitary channel sizes consistent with the induced connexin expression. In cells with induced expression of either Cx40 or Cx37, intercellular transfer of microinjected Lucifer yellow was reduced, but transfer of NBD-TMA (2-(4-nitro-2,1,3-benzoxadiol-7-yl)[aminoethyl]trimethylammonium) was not affected. In cocultures containing uninduced EcR cells together with cells induced to coexpress Cx37 or Cx40, Lucifer yellow transfer was observed only between the cells expressing Cx43 alone. These data show that induced expression of either Cx37 or Cx40 in Cx43-expressing cells can selectively alter the intercellular exchange of some molecules without affecting the transfer of others. 相似文献
122.
L. J. Baumgartner M. Bettanin J. McPherson M. Jones B. Zampatti K. Beyer 《Zeitschrift fur angewandte Ichthyologie》2012,28(4):531-536
This study aimed to ascertain the influence of turbidity and migration rate on the count accuracy and size determination of an automatic infrared fish counter. The effect of turbidity on enumerating silver perch (Bidyanus bidyanus) migration rates was insignificant when compared to the inability of the infrared counter to deal with large numbers of migrating fish. The infrared counter underestimated counts by 56–84% at moderate migration rates (12 fish h?1) and by 62–82% at the highest migration rate (120 fish h?1). When multiple fish were simultaneously passed through the counter, the software detected them as a single fish and overestimated fish length. Fish passed through the unit ranged from 340 to 520 mm but the infrared counter estimated the range to be 140–780 mm, with the lengths of a high proportion of individuals being underestimated. Most issues of inaccuracy appeared to be software‐related and could be overcome with further software development. Further assessment of the applicability of the unit to enumerate fish migration, at high migration rates, should then be considered. 相似文献
123.
Beyer T Danilchik M Thumberger T Vick P Tisler M Schneider I Bogusch S Andre P Ulmer B Walentek P Niesler B Blum M Schweickert A 《Current biology : CB》2012,22(1):33-39
In vertebrates, most inner organs are asymmetrically arranged with respect to the main body axis [1]. Symmetry breakage in fish, amphibian, and mammalian embryos depends on cilia-driven leftward flow of extracellular fluid during neurulation [2-5]. Flow induces the asymmetric nodal cascade that governs asymmetric organ morphogenesis and placement [1, 6, 7]. In the frog Xenopus, an alternative laterality-generating mechanism involving asymmetric localization of serotonin at the 32-cell stage has been proposed [8]. However, no functional linkage between this early localization and flow at neurula stage has emerged. Here, we report that serotonin signaling is required for specification of the superficial mesoderm (SM), which gives rise to the ciliated gastrocoel roof plate (GRP) where flow occurs [5, 9]. Flow and asymmetry were lost in embryos in which serotonin signaling was downregulated. Serotonin, which we found uniformly distributed along the main body axes in the early embryo, was required for Wnt signaling, which provides the instructive signal to specify the GRP. Importantly, serotonin was required for Wnt-induced double-axis formation as well. Our data confirm flow as primary mechanism of symmetry breakage and suggest a general role of serotonin as competence factor for Wnt signaling during axis formation in Xenopus. 相似文献
124.
Elizabeth A. Stoll Svetlana A. Mikheeva Richard P. Beyer David A. Plotnik Jeffrey L. Schwartz Jason K. Rockhill John R. Silber Donald E. Born Yoshito Kosai Philip J. Horner Robert C. Rostomily 《Aging cell》2012,11(6):1027-1035
Increasing age is the most robust predictor of greater malignancy and treatment resistance in human gliomas. However, the adverse association of clinical course with aging is rarely considered in animal glioma models, impeding delineation of the relative importance of organismal versus progenitor cell aging in the genesis of glioma malignancy. To address this limitation, we implanted transformed neural stem/progenitor cells (NSPCs), the presumed cells of glioma origin, from 3‐ and 18‐month‐old mice into 3‐ and 20‐month host animals. Transplantation with progenitors from older animals resulted in significantly shorter (P ≤ 0.0001) median survival in both 3‐month (37.5 vs. 83 days) and 20‐month (38 vs. 67 days) hosts, indicating that age‐dependent changes intrinsic to NSPCs rather than host animal age accounted for greater malignancy. Subsequent analyses revealed that increased invasiveness, genomic instability, resistance to therapeutic agents, and tolerance to hypoxic stress accompanied aging in transformed NSPCs. Greater tolerance to hypoxia in older progenitor cells, as evidenced by elevated HIF‐1 promoter reporter activity and hypoxia response gene (HRG) expression, mirrors the upregulation of HRGs in cohorts of older vs. younger glioma patients revealed by analysis of gene expression databases, suggesting that differential response to hypoxic stress may underlie age‐dependent differences in invasion, genomic instability, and treatment resistance. Our study provides strong evidence that progenitor cell aging is responsible for promoting the hallmarks of age‐dependent glioma malignancy and that consideration of progenitor aging will facilitate development of physiologically and clinically relevant animal models of human gliomas. 相似文献
125.
126.
Jinghai Chen Steven B. Ortmeier Olga V. Savinova Vijaya B. Nareddy April J. Beyer Dajun Wang A. Martin Gerdes 《Journal of cellular and molecular medicine》2012,16(11):2726-2735
Study of physiological angiogenesis and associated signalling mechanisms in adult heart has been limited by the lack of a robust animal model. We investigated thyroid hormone‐induced sprouting angiogenesis and the underlying mechanism. Hypothyroidism was induced in C57BL/6J mice by feeding with propylthiouracil (PTU). One year of PTU treatment induced heart failure. Both 12 weeks‐ (young) and 1 year‐PTU (middle age) treatment caused a remarkable capillary rarefaction observed in capillary density. Three‐day Triiodothyronine (T3) treatment significantly induced cardiac capillary growth in hypothyroid mice. In cultured left ventricle (LV) tissues from PTU‐treated mice, T3 also induced robust sprouting angiogenesis where pericyte‐wrapped endothelial cells formed tubes. The in vitro T3 angiogenic response was similar in mice pre‐treated with PTU for periods ranging from 1.5 to 12 months. Besides bFGF and VEGF164, PDGF‐BB was the most robust angiogenic growth factor, which stimulated notable sprouting angiogenesis in cultured hypothyroid LV tissues with increasing potency, but had little effect on tissues from euthyroid mice. T3 treatment significantly increased PDGF receptor beta (PDGFR‐β) protein levels in hypothyroid heart. PDGFR inhibitors blocked the action of T3 both on sprouting angiogenesis in cultured LV tissue and on capillary growth in vivo. In addition, activation of Akt signalling mediated in T3‐induced angiogenesis was blocked by PDGFR inhibitor and neutralizing antibody. Our results suggest that hypothyroidism leads to cardiac microvascular impairment and rarefaction with increased sensitivity to angiogenic growth factors. T3‐induced cardiac sprouting angiogenesis in adult hypothyroid mice was associated with PDGF‐BB, PDGFR‐β and downstream activation of Akt. 相似文献
127.
In innate immunity, dead and dying cells release internal constituents that can serve as damage-associated molecular patterns (DAMPs) or alarmins. This release occurs more abundantly during necrosis than apoptosis and may account for the differences in the immunologic properties of these death forms. To elucidate DAMP release in necrosis, we compared the levels of two nuclear molecules (DNA and HMGB1, a non-histone protein with alarmin activity) in media following necrosis of Jurkat T cells by freeze-thawing, ethanol, heat or hydrogen peroxide treatment. In our experiments, DNA release was measured by fluorimetry with the dye PicoGreen, while HMGB1 was measured by Western blotting. As the results of our study show, each form of necrosis is associated with a distinct pattern of DNA and HMGB1 release with respect to kinetics and amounts. Of these, freeze-thawing produced the highest and most rapid increase in HMGB1 and DNA levels, although the released DNA was subject to nuclease digestion; in addition, freeze-thawing led to the production of particles measured by flow cytometry. Together, these results indicate that experimental necrosis leads to diverse patterns of nuclear molecule release which could affect their immunologic activity. 相似文献
128.
Popov A Driesen J Abdullah Z Wickenhauser C Beyer M Debey-Pascher S Saric T Kummer S Takikawa O Domann E Chakraborty T Krönke M Utermöhlen O Schultze JL 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(7):4976-4988
Myeloid dendritic cells (DC) and macrophages play an important role in pathogen sensing and antimicrobial defense. In this study we provide evidence that myeloid DC respond to infection with Listeria monocytogenes with simultaneous induction of multiple stimulatory and inhibitory molecules. However, the overall impact of infected DC during T cell encounter results in suppression of T cell activation, indicating that inhibitory pathways functionally predominate. Inhibitory activity of infected DC is effected mainly by IL-10 and cyclooxygenase 2-mediated mechanisms, with soluble CD25 acting as an IL-2 scavenger as well as by the products of tryptophan catabolism. These inhibitory pathways are strictly TNF-dependent. In addition to direct infection, DC bearing this regulatory phenotype can be induced in vitro by a combination of signals including TNF, TLR2, and prostaglandin receptor ligation and by supernatants derived from the infected cells. Both infection-associated DC and other in vitro-induced regulatory DC are characterized by increased resistance to infection and enhanced bactericidal activity. Furthermore, myeloid DC expressing multiple regulatory molecules are identified in vivo in granuloma during listeriosis and tuberculosis. Based on the in vivo findings and the study of in vitro models, we propose that in granulomatous infections regulatory DC may possess dual function evolved to protect the host from disseminating infection via inhibition of granuloma destruction by T cells and control of pathogen spreading. 相似文献
129.
130.
Huge V Lauchart M Förderreuther S Kaufhold W Valet M Azad SC Beyer A Magerl W 《PloS one》2008,3(7):e2742