全文获取类型
收费全文 | 21329篇 |
免费 | 1498篇 |
国内免费 | 11篇 |
专业分类
22838篇 |
出版年
2024年 | 27篇 |
2023年 | 66篇 |
2022年 | 242篇 |
2021年 | 413篇 |
2020年 | 247篇 |
2019年 | 310篇 |
2018年 | 531篇 |
2017年 | 393篇 |
2016年 | 680篇 |
2015年 | 1126篇 |
2014年 | 1223篇 |
2013年 | 1393篇 |
2012年 | 1825篇 |
2011年 | 1706篇 |
2010年 | 1098篇 |
2009年 | 912篇 |
2008年 | 1344篇 |
2007年 | 1184篇 |
2006年 | 1052篇 |
2005年 | 971篇 |
2004年 | 958篇 |
2003年 | 777篇 |
2002年 | 784篇 |
2001年 | 627篇 |
2000年 | 632篇 |
1999年 | 422篇 |
1998年 | 166篇 |
1997年 | 129篇 |
1996年 | 119篇 |
1995年 | 87篇 |
1994年 | 82篇 |
1993年 | 69篇 |
1992年 | 157篇 |
1991年 | 125篇 |
1990年 | 88篇 |
1989年 | 103篇 |
1988年 | 70篇 |
1987年 | 65篇 |
1986年 | 69篇 |
1985年 | 53篇 |
1984年 | 47篇 |
1983年 | 37篇 |
1982年 | 27篇 |
1981年 | 24篇 |
1978年 | 28篇 |
1976年 | 32篇 |
1975年 | 29篇 |
1973年 | 33篇 |
1971年 | 23篇 |
1969年 | 24篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
951.
Mutations in both gp120 and gp41 Are Responsible for the Broad Neutralization Resistance of Variant Human Immunodeficiency Virus Type 1 MN to Antibodies Directed at V3 and Non-V3 Epitopes 总被引:2,自引:6,他引:2 下载免费PDF全文
Eun Ju Park Luba K. Vujcic Rita Anand Theodore S. Theodore Gerald V. Quinnan Jr. 《Journal of virology》1998,72(9):7099-7107
The escape of human immunodeficiency virus type 1 from effects of neutralizing antibodies was studied by using neutralization-resistant (NR) variants generated by growing the neutralization-sensitive (NS) wild-type MN virus in the presence of human serum with neutralizing antibodies, more than 99% of which were directed at the V3 region of gp120. The variants obtained had broad neutralization resistance to human sera, without limitation with respect to the V3 specificity of the sera. The molecular basis for the resistance was evaluated with molecularly cloned viruses, as well as with pseudoviruses expressing envelope glycoproteins of the NS and NR phenotypes. Nucleotide sequence analyses comparing NS and NR clones revealed a number of polymorphisms, including six in the V1/V2 region, two in C4/V5 of gp120, three in the leucine zipper (LZ) domain of gp41, and two in the second external putative α-helix region of gp41. A series of chimeras from NS and NR env genes was constructed, and each was presented on pseudoviruses to locate the domain(s) which conferred the phenotypic changes. The neutralization phenotypes of the chimeric clones were found to be dependent on mutations in both the C4/V5 region of gp120 and the LZ region of gp41. Additionally, interaction between mutations in gp120 and gp41 was demonstrated in that a chimeric env gene consisting of a gp120 coding sequence from an NS clone and a gp41 sequence from an NR clone yielded a pseudovirus with minimal infectivity. The possible significance of predicted amino acid changes in these domains is discussed. The results indicate that polyvalent antibodies predominantly directed against V3 can induce NR through selection for mutations that alter interactions of other domains in the envelope complex. 相似文献
952.
Drosophila perlecan modulates FGF and hedgehog signals to activate neural stem cell division 总被引:3,自引:0,他引:3
Park Y Rangel C Reynolds MM Caldwell MC Johns M Nayak M Welsh CJ McDermott S Datta S 《Developmental biology》2003,253(2):247-257
Mutations in the Drosophila trol gene cause cell cycle arrest of neuroblasts in the larval brain. Here, we show that trol encodes the Drosophila homolog of Perlecan and regulates neuroblast division by modulating both FGF and Hh signaling. Addition of human FGF-2 to trol mutant brains in culture rescues the trol proliferation phenotype, while addition of a MAPK inhibitor causes cell cycle arrest of the regulated neuroblasts in wildtype brains. Like FGF, Hh activates stem cell division in the larval brain in a Trol-dependent fashion. Coimmunoprecipitation studies are consistent with interactions between Trol and Hh and between mammalian Perlecan and Shh that are not competed with heparin sulfate. Finally, analyses of mutations in trol, hh, and ttv suggest that Trol affects Hh movement. These results indicate that Trol can mediate signaling through both of the FGF and Hedgehog pathways to control the onset of stem cell proliferation in the developing nervous system. 相似文献
953.
Dan?Bolser Panos?Dafas Richard?Harrington Jong?Park Michael?SchroederEmail author 《BMC bioinformatics》2003,4(1):45
Background
Large-scale protein interaction maps provide a new, global perspective with which to analyse protein function. PSIMAP, the Protein Structural Interactome Map, is a database of all the structurally observed interactions between superfamilies of protein domains with known three-dimensional structure in the PDB. PSIMAP incorporates both functional and evolutionary information into a single network. 相似文献954.
Caveolin-1 null (-/-) mice show dramatic reductions in life span 总被引:7,自引:0,他引:7
Park DS Cohen AW Frank PG Razani B Lee H Williams TM Chandra M Shirani J De Souza AP Tang B Jelicks LA Factor SM Weiss LM Tanowitz HB Lisanti MP 《Biochemistry》2003,42(51):15124-15131
Caveolae are 50-100 nm flask-shaped invaginations of the plasma membrane found in most cell types. Caveolin-1 is the principal protein component of caveolae membranes in nonmuscle cells. The recent development of Cav-1-deficient mice has allowed investigators to study the in vivo functional role of caveolae in the context of a whole animal model, as these mice lack morphologically detectable caveolae membrane domains. Surprisingly, Cav-1 null mice are both viable and fertile. However, it remains unknown whether loss of caveolin-1 significantly affects the overall life span of these animals. To quantitatively determine whether loss of Cav-1 gene expression confers any survival disadvantages with increasing age, we generated a large cohort of mice (n = 180), consisting of Cav-1 wild-type (+/+) (n = 53), Cav-1 heterozygous (+/-) (n = 70), and Cav-1 knockout (-/-) (n = 57) animals, and monitored their long-term survival over a 2 year period. Here, we show that Cav-1 null (-/-) mice exhibit an approximately 50% reduction in life span, with major declines in viability occurring between 27 and 65 weeks of age. However, Cav-1 heterozygous (+/-) mice did not show any changes in long-term survival, indicating that loss of both Cav-1 alleles is required to mediate a reduction in life span. Mechanistically, these dramatic reductions in life span appear to be secondary to a combination of pulmonary fibrosis, pulmonary hypertension, and cardiac hypertrophy in Cav-1 null mice. Taken together, our results provide the first demonstration that loss of Cav-1 gene expression and caveolae organelles dramatically affects the long-term survival of an organism. In addition, aged Cav-1 null mice may provide a new animal model to study the pathogenesis and treatment of progressive hypertrophic cardiomyopathy and sudden cardiac death syndrome. 相似文献
955.
Han Seungsu Lee Yeongmok Park Eun Joo Min Myung Ki Lee Yongsang Kim Tae-Houn Kim Beom-Gi Lee Sangho 《Plant molecular biology》2019,100(3):319-333
Plant Molecular Biology - We determined the structure of OsPYL/RCAR3:OsPP2C50 complex with pyrabactin. Our results suggest that a less-conserved phenylalanine of OsPYL/RCAR subfamily I is... 相似文献
956.
Park Soomin Steen Collin J. Fischer Alexandra L. Fleming Graham R. 《Photosynthesis research》2019,141(3):367-376
Photosynthesis Research - Although the importance of nonphotochemical quenching (NPQ) on photosynthetic biomass production and crop yields is well established, the in vivo operation of the... 相似文献
957.
In wireless sensor networks, when a sensor node detects events in the surrounding environment, the sensing period for learning
detailed information is likely to be short. However, the short sensing cycle increases the data traffic of the sensor nodes
in a routing path. Since the high traffic load causes a data queue overflow in the sensor nodes, important information about
urgent events could be lost. In addition, since the battery energy of the sensor nodes is quickly exhausted, the entire lifetime
of wireless sensor networks would be shortened. In this paper, to address these problem issues, a new routing protocol is
proposed based on a lightweight genetic algorithm. In the proposed method, the sensor nodes are aware of the data traffic
rate to monitor the network congestion. In addition, the fitness function is designed from both the average and the standard
deviation of the traffic rates of sensor nodes. Based on dominant gene sets in a genetic algorithm, the proposed method selects
suitable data forwarding sensor nodes to avoid heavy traffic congestion. In experiments, the proposed method demonstrates
efficient data transmission due to much less queue overflow and supports fair data transmission for all sensor nodes. From
the results, it is evident that the proposed method not only enhances the reliability of data transmission but also distributes
the energy consumption across wireless sensor networks. 相似文献
958.
959.
Young Mi Park 《BMB reports》2015,48(1):48-53
Oxidized LDL (oxLDL) performs critical roles in atherosclerosis by inducing macrophage foam cell formation and promoting inflammation. There have been reports showing that oxLDL modulates macrophage cytoskeletal functions for oxLDL uptake and trapping, however, the precise mechanism has not been clearly elucidated. Our study examined the effect of oxLDL on non-muscle myosin heavy chain IIA (MHC-IIA) in macrophages. We demonstrated that oxLDL induces phosphorylation of MHC-IIA (Ser1917) in peritoneal macrophages from wild-type mice and THP-1, a human monocytic cell line, but not in macrophages deficient for CD36, a scavenger receptor for oxLDL. Protein kinase C (PKC) inhibitor-treated macrophages did not undergo the oxLDL-induced MHC-IIA phosphorylation. Our immunoprecipitation revealed that oxLDL increased physical association between PKC and MHC-IIA, supporting the role of PKC in this process. We conclude that oxLDL via CD36 induces PKC-mediated MHC-IIA (Ser1917) phosphorylation and this may affect oxLDL-induced functions of macrophages involved in atherosclerosis. [BMB Reports 2015; 48(1): 48-53] 相似文献
960.
Lee S Park JB Kim JH Kim Y Kim JH Shin KJ Lee JS Ha SH Suh PG Ryu SH 《The Journal of biological chemistry》2001,276(30):28252-28260
Mammalian phospholipase D (PLD) plays a key role in several signal transduction pathways and is involved in many diverse functions. To elucidate the complex molecular regulation of PLD, we investigated PLD-binding proteins obtained from rat brain extract. Here we report that a 43-kDa protein in the rat brain, beta-actin, acts as a major PLD2 direct-binding protein as revealed by peptide mass fingerprinting in combination with matrix-assisted laser desorption ionization/time-of-flight mass spectrometry. We also determined that the region between amino acids 613 and 723 of PLD2 is required for the direct binding of beta-actin, using bacterially expressed glutathione S-transferase fusion proteins of PLD2 fragments. Intriguingly, purified beta-actin potently inhibited both phosphatidylinositol-4,5-bisphosphate- and oleate-dependent PLD2 activities in a concentration-dependent manner (IC50 = 5 nm). In a previous paper, we reported that alpha-actinin inhibited PLD2 activity in an interaction-dependent and an ADP-ribosylation factor 1 (ARF1)-reversible manner (Park, J. B., Kim, J. H., Kim, Y., Ha, S. H., Kim, J. H., Yoo, J.-S., Du, G., Frohman, M. A., Suh, P.-G., and Ryu, S. H. (2000) J. Biol. Chem. 275, 21295-21301). In vitro binding analyses showed that beta-actin could displace alpha-actinin binding to PLD2, demonstrating independent interaction between cytoskeletal proteins and PLD2. Furthermore, ARF1 could steer the PLD2 activity in a positive direction regardless of the inhibitory effect of beta-actin on PLD2. We also observed that beta-actin regulates PLD1 and PLD2 with similar binding and inhibitory potencies. Immunocytochemical and co-immunoprecipitation studies demonstrated the in vivo interaction between the two PLD isozymes and actin in cells. Taken together, these results suggest that the regulation of PLD by cytoskeletal proteins, beta-actin and alpha-actinin, and ARF1 may play an important role in cytoskeleton-related PLD functions. 相似文献