全文获取类型
收费全文 | 9293篇 |
免费 | 833篇 |
国内免费 | 17篇 |
专业分类
10143篇 |
出版年
2023年 | 42篇 |
2022年 | 110篇 |
2021年 | 162篇 |
2020年 | 116篇 |
2019年 | 145篇 |
2018年 | 198篇 |
2017年 | 190篇 |
2016年 | 266篇 |
2015年 | 484篇 |
2014年 | 487篇 |
2013年 | 602篇 |
2012年 | 734篇 |
2011年 | 663篇 |
2010年 | 430篇 |
2009年 | 413篇 |
2008年 | 576篇 |
2007年 | 515篇 |
2006年 | 455篇 |
2005年 | 421篇 |
2004年 | 392篇 |
2003年 | 357篇 |
2002年 | 327篇 |
2001年 | 185篇 |
2000年 | 168篇 |
1999年 | 139篇 |
1998年 | 82篇 |
1997年 | 68篇 |
1996年 | 54篇 |
1995年 | 78篇 |
1994年 | 45篇 |
1993年 | 55篇 |
1992年 | 88篇 |
1991年 | 75篇 |
1990年 | 79篇 |
1989年 | 84篇 |
1988年 | 81篇 |
1987年 | 76篇 |
1986年 | 65篇 |
1985年 | 74篇 |
1984年 | 52篇 |
1983年 | 45篇 |
1982年 | 34篇 |
1980年 | 29篇 |
1979年 | 48篇 |
1978年 | 43篇 |
1977年 | 29篇 |
1976年 | 41篇 |
1975年 | 32篇 |
1974年 | 32篇 |
1973年 | 26篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
151.
CD4-independent, productive human immunodeficiency virus type 1 infection of hepatoma cell lines in vitro. 总被引:10,自引:6,他引:10 下载免费PDF全文
Y Z Cao A E Friedman-Kien Y X Huang X L Li M Mirabile T Moudgil D Zucker-Franklin D D Ho 《Journal of virology》1990,64(6):2553-2559
Five hepatoma cell lines, including CZHC/8571, PLC/PRF/5, Hep3B, HepG2, and HUH7, were inoculated with three diverse isolates of human immunodeficiency virus type 1 (HIV-1). Productive infection was noted in all hepatoma cell lines, and expression of viral p24 antigen lasted for over 3 months, but its level decreased in proportion to the number of viable cells. HIV-1 antigens were also found in the cells by immunohistochemical staining and radioimmunoprecipitation assay, as were viral RNA by in situ hybridization and HIV-1-like particles by electron microscopy. Virus yield assays were also positive on supernatant fluids collected from hepatoma cultures inoculated with HIV-1. Despite their susceptibility to infection, all five hepatoma cell lines were negative for CD4 by immunofluorescence and for CD4 mRNA by slot-blot hybridization. In addition, HIV-1 infection of hepatoma cell lines was not blocked by anti-CD4 monoclonal antibody or soluble CD4. Together, these findings clearly demonstrate that all five hepatoma cell lines were susceptible to productive infection by HIV-1 in vitro via a CD4-independent mechanism. 相似文献
152.
The effects of continuous infusion of NMDA receptor antagonist MK-801 on the modulation of NMDA receptor subunits NR1, NR2A, NR2B, and NR2C were investigated by using in situ hybridization study. Differential assembly of NMDA receptor subunits determines their functional characteristics. Continuous intracerebroventricular (i.c.v.) infusion with MK-801 (1 pmol/10 l/h) for 7 days resulted in significant modulations in the NR1, NR2A, and NR2B mRNA levels without producing stereotypic motor syndromes. The levels of NR1 mRNA were significantly increased (9-20%) in the cerebral cortex, striatum, septum, and CA1 of hippocampus in MK-801-infused rats. The levels of NR2A mRNA were significantly decreased (11-16%) in the CA3 and dentate gyrus of hippocampus in MK-801-infused rats. In contrast to NR2A, NR2B subunit mRNA levels were increased (10-14%) in the cerebral cortex, caudate putamen, and thalamus. However, no changes of NR2C subunits in cerebellar granule layer were observed. Using quantitative ligand autoradiography, the binding of NMDA receptor ligand [3H]MK-801 was increased (12-25%) significantly in almost all brain regions except in the thalamus and cerebellum after 7 days infusion with MK-801. These results suggest that region-specific changes of NMDA receptor subunit mRNA and [3H]MK-801 binding are involved in the MK-801-infused adult rats. 相似文献
153.
Rohatgi R Nollau P Ho HY Kirschner MW Mayer BJ 《The Journal of biological chemistry》2001,276(28):26448-26452
The Wiskott-Aldrich syndrome protein (WASP) and its relative neural WASP (N-WASP) regulate the nucleation of actin filaments through their interaction with the Arp2/3 complex and are regulated in turn by binding to GTP-bound Cdc42 and phosphatidylinositol 4,5-bisphosphate. The Nck Src homology (SH) 2/3 adaptor binds via its SH3 domains to a proline-rich region on WASP and N-WASP and has been implicated in recruitment of these proteins to sites of tyrosine phosphorylation. We show here that Nck SH3 domains dramatically stimulate the rate of nucleation of actin filaments by purified N-WASP in the presence of Arp2/3 in vitro. All three Nck SH3 domains are required for maximal activation. Nck-stimulated actin nucleation by N-WASP.Arp2/3 complexes is further stimulated by phosphatidylinositol 4,5-bisphosphate, but not by GTP-Cdc42, suggesting that Nck and Cdc42 activate N-WASP by redundant mechanisms. These results suggest the existence of an Nck-dependent, Cdc42-independent mechanism to induce actin polymerization at tyrosine-phosphorylated Nck binding sites. 相似文献
154.
M F Ho A P Monaco L A Blonden G J van Ommen N A Affara M A Ferguson-Smith H Lehrach 《American journal of human genetics》1992,50(2):317-330
McLeod syndrome, characterized by acanthocytosis and the absence of a red-blood-cell Kell antigen (Kx), is a multisystem disorder involving a late-onset myopathy, splenomegaly, and neurological defects. The locus for this syndrome has been mapped, by deletion analysis, to a region between the loci for Duchenne muscular dystrophy (DMD) and chronic granulomatous disease (CGD). In this study, we describe a new marker, 3BH/R 0.3 (DXS 709), isolated by cloning the deletion breakpoint of a DMD patient. A long-range restriction map of Xp21, encompassing the gene loci for McLeod and CGD, was constructed, and multiple CpG islands were found clustered in a 700-kb region. Using the new marker, we have limited the McLeod syndrome critical region to 150-380-kb. Within this interval, two CpG-rich islands which may represent candidate sites for the McLeod gene were identified. 相似文献
155.
Y. B. Ho 《Hydrobiologia》1981,77(1):43-47
The amounts of tissue nitrogen, phosphorus, potassium, sodium, calcium and iron were estimated in the green alga Ulva lactuca L. collected from 9 rural and 14 urban littoral sites in the waters around Hong Kong Island during 1978 and 1979. The mean levels of tissue nitrogen and phosphorus were respectively 65% and 87% more in urban sites than in rural ones. Very significant correlation (r = 0.920) was found between the logarithmic concentration of seawater inorganic nitrogen and that of tissue nitrogen. The same applied to soluble reactive phosphorus in seawater and tissue phosphorus (r = 0.886). The levels of potassium, sodium and calcium in the alga were relatively uniform. However considerable variation in the level of iron was detected. The potential use of Ulva as an indicator species for eutrophication is discussed. 相似文献
156.
Insulin antagonism of glucocorticoid induction of tyrosine aminotransferase in cultured foetal hepatocytes 总被引:7,自引:0,他引:7
Polyadenylated RNA from developing Artemia salina cysts was fractionated by centrifugation through a sucrose gradient containing methylmercuric hydroxide (CH3HgOH). Aliquots of each fraction were directly added to a rabbit reticulocyte lysate to program protein synthesis in vitro. The translation products were assayed for eukaryotic elongation factor Tu (eEF-Tu) by immunoprecipitation with an antibody raised in rabbits and purified by affinity chromatography. The immunoprecipitated radioactivity was analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecylsulphate. Sequences coding for eEF-Tu sediment in the 20-S region of the gradient and form a major component of the poly(A)-containing RNA. The mRNA of the 20-S region, comprising about 10% of the poly(a)-containing RNA fractionated on the gradient, has been translated in vitro and 30% of the translation products represent immunoprecipitable eEF-Tu protein chains with an Mr of 50000. 相似文献
157.
Kiyoshi Takahashi Katsuya Miyatani Hiroyuki Yanai Ho Jong Jeon Kotaro Fujiwara Tadashi Yoshino Kazuhiko Hayashi Tadaatsu Akagi Ken Tsutsui Koichi Mizobuchi 《Virchows Archiv. B, Cell pathology including molecular pathology》1992,62(1):105-113
Monocytic leukemia (MoL) cells were obtained from the peripheral blood of a patient in whom the leukemic cells infiltrating
various lymphoreticular organs exhibited features intermediate between interdigitating reticulum cells (IDC) and ordinary
phagocytic macrophages, whereas the leukemic cells in the peripheral blood were essentially monocytic and lacked such features.
Peripheral blood CD4+ T-cells were established as an interleukin-2-dependent T-cell line. When the MoL cells were exposed
for a few days to conditioned medium from the T-cell line, they extended several dendritic cytoplasmic projections and became
intensely positive for HLA-DR antigen, cytoplasmic S-100β protein, and CD1 antigen. Functionally, the conditioned medium significantly
down-regulated Fc-mediated and Fc-independent phagocytic activities, and the levels of lysosomal enzymes such as lysozyme
and nonspecific esterase in the MoL cells. Moreover, the conditioned medium significantly up-regulated the accessory cell
function of the MoL cells as measured by the primary allogenic mixed leukocyte reaction (MLR). Furthermore, the conditioned
medium significantly down-regulated the expression of CD14 antigen.
Biochemical analysis indicated that the factor responsible for these changes is a protein which is distinct from known human
cytokines and whose molecular weight is approximately 31 kDa. These findings suggest that IDC are closely related the monocytic
lineage and that helper T-cells play an important role in constructing the microenvironment of T-lymphoid tissues which is
necessary for the differentiation and maturation of IDC. 相似文献
158.
ZAKβ antagonizes and ameliorates the cardiac hypertrophic and apoptotic effects induced by ZAKα 下载免费PDF全文
Chien‐Yao Fu Wei‐Wen Kuo Tsung‐Jung Ho Su‐Ying Wen Ling‐Chun Lin Yan‐Shen Tseng Hui‐Chuan Hung Vijaya Padma Viswanadha Chih‐Yang Huang 《Cell biochemistry and function》2016,34(8):606-612
ZAK (sterile alpha motif and leucine zipper containing kinase AZK), a serine/threonine kinase with multiple biochemical functions, has been associated with various cell processes, including cell proliferation, cell differentiation, and cardiac hypertrophy. In our previous reports, we found that the activation of ZAKα signaling was critical for cardiac hypertrophy. In this study, we show that the expression of ZAKα activated apoptosis through both a FAS‐dependent pathway and a mitochondria‐dependent pathway by subsequently inducing caspase‐3. ZAKβ, an isoform of ZAKα, is dramatically expressed during cardiac hypertrophy and apoptosis. The interaction between ZAKα and ZAKβ was demonstrated here using immunoprecipitation. The results show that ZAKβ has the ability to diminish the expression level of ZAKα. These findings reveal an inherent regulatory role of ZAKβ to antagonize ZAKα and to subsequently downregulate the cardiac hypertrophy and apoptosis induced by ZAKα. 相似文献
159.
Optimal induction of T-cell responses against hepatitis C virus E2 by antigen engineering in DNA immunization 总被引:3,自引:0,他引:3
Although DNA immunization is a safe and efficient method for inducing cellular immune responses, it generates relatively weak and slow immune responses. Here, we investigated the effect of hepatitis C virus (HCV) antigen modifications on the induction of T-cell responses in DNA immunization. It is likely that the strength of T-cell responses has an inverse relationship with the length of the insert DNA. Interestingly, a mixture of several plasmids carrying each gene induced a higher level of T-cell responses than a single plasmid expressing a long polyprotein. Moreover, the presence of a transmembrane domain in HCV E2 resulted in stronger T-cell responses against E2 protein than its absence. Taken together, our results indicate that the tailored modifications of DNA-encoded antigens are capable of optimizing the induction of T-cell responses which is required for eliminating the cells chronically infected with highly variable viruses such as HCV and human immunodeficiency virus. 相似文献
160.
A functional interaction between chromogranin B and the inositol 1,4,5-trisphosphate receptor/Ca2+ channel 总被引:2,自引:0,他引:2
Thrower EC Choe CU So SH Jeon SH Ehrlich BE Yoo SH 《The Journal of biological chemistry》2003,278(50):49699-49706
Chromogranins A and B (CGA and CGB) are high capacity, low affinity calcium (Ca2+) storage proteins found in many cell types most often associated with secretory granules of secretory cells but also with the endoplasmic reticulum (ER) lumen of these cells. Both CGA and CGB associate with inositol 1,4,5-trisphosphate receptor (InsP3R) in a pH-dependent manner. At an intraluminal pH of 5.5, as found in secretory vesicles, both CGA and CGB bind to the InsP3R. When the intraluminal pH is 7.5, as found in the ER, CGA totally dissociates from InsP3R, whereas CGB only partially dissociates. To investigate the functional consequences of the interaction between the InsP3R and CGB monomers or CGA/CGB heteromers, purified mouse InsP3R type I were fused to planar lipid bilayers and activated by 2 microM InsP3. In the presence of luminal CGB monomers or CGA/CGB heteromers the InsP3R/Ca2+ channel open probability and mean open time increased significantly. The channel activity remained elevated when the pH was changed to 7.5, a reflection of CGB binding to the InsP3R even at pH 7.5. These results suggest that CGB may play an important modulatory role in the control of Ca2+ release from the ER. Furthermore, the difference in the ability of CGA and CGB to regulate the InsP3R/Ca2+ channel and the variability of CGA/CGB ratios could influence the pattern of InsP3-mediated Ca2+ release. 相似文献