全文获取类型
收费全文 | 28862篇 |
免费 | 82篇 |
国内免费 | 158篇 |
专业分类
系统科学 | 139篇 |
丛书文集 | 499篇 |
教育与普及 | 42篇 |
理论与方法论 | 100篇 |
现状及发展 | 13451篇 |
研究方法 | 1278篇 |
综合类 | 13197篇 |
自然研究 | 396篇 |
出版年
2013年 | 269篇 |
2012年 | 411篇 |
2011年 | 809篇 |
2010年 | 168篇 |
2008年 | 523篇 |
2007年 | 576篇 |
2006年 | 576篇 |
2005年 | 535篇 |
2004年 | 538篇 |
2003年 | 498篇 |
2002年 | 499篇 |
2001年 | 936篇 |
2000年 | 865篇 |
1999年 | 616篇 |
1992年 | 595篇 |
1991年 | 414篇 |
1990年 | 486篇 |
1989年 | 494篇 |
1988年 | 460篇 |
1987年 | 546篇 |
1986年 | 474篇 |
1985年 | 596篇 |
1984年 | 484篇 |
1983年 | 364篇 |
1982年 | 340篇 |
1981年 | 367篇 |
1980年 | 462篇 |
1979年 | 889篇 |
1978年 | 757篇 |
1977年 | 740篇 |
1976年 | 611篇 |
1975年 | 632篇 |
1974年 | 845篇 |
1973年 | 756篇 |
1972年 | 779篇 |
1971年 | 840篇 |
1970年 | 1073篇 |
1969年 | 813篇 |
1968年 | 820篇 |
1967年 | 795篇 |
1966年 | 681篇 |
1965年 | 472篇 |
1964年 | 156篇 |
1959年 | 249篇 |
1958年 | 440篇 |
1957年 | 292篇 |
1956年 | 259篇 |
1955年 | 246篇 |
1954年 | 239篇 |
1948年 | 162篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
751.
Cross-talk between cellular signalling pathways suggested by phorbol-ester-induced adenylate cyclase phosphorylation 总被引:8,自引:0,他引:8
Receptor-mediated activation of both adenylate cyclase and phosphatidylinositide hydrolysis systems occurs through guanine nucleotide regulatory proteins and ultimately leads to specific activation of either cyclic AMP-dependent protein kinase A or Ca2+/phospholipid-dependent protein kinase C. Given the remarkable diversity of agents that influence cellular metabolism through these pathways and the similarities of their components, interactions between the two signalling systems could occur. In fact, stimulation of cells with 12-O-tetradecanoyl phorbol-13-acetate (TPA), a phorbol ester that activates protein kinase C, influences hormone-sensitive adenylate cyclase. In some cells TPA induces desensitization of receptor-mediated stimulation of adenylate cyclase, whereas in others, such as frog erythrocytes, phorbol ester treatment results in increased agonist-stimulated as well as basal, guanine nucleotide- and fluoride ion-stimulated adenylate cyclase activities. We show here that TPA produces phosphorylation of the catalytic unit of adenylate cyclase in frog erythrocytes. Moreover, purified protein kinase C can directly phosphorylate in vitro the catalytic unit of adenylate cyclase purified from bovine brain. These results suggest that phosphorylation of the catalytic unit of adenylate cyclase by protein kinase C may be involved in the phorbol ester-induced enhancement of adenylate cyclase activity. In addition to providing the first direct demonstration of a covalent modification of the catalytic unit of adenylate cyclase, these results provide a potential biochemical mechanism for a regulatory link between the two major transmembrane signalling systems. 相似文献
752.
Cells which can suppress the immune response to an antigen (TS cells) appear to be essential for regulation of the immune system. But the characterization of the TS lineage has not been extensive and many are sceptical of studies using uncloned or hybrid T-cell lines. The nature of the antigen receptor on these cells is unclear. T cells of the helper or cytotoxic lineages appear to recognize their targets using the T-cell receptor (TCR) alpha beta-CD3 complex. TCR beta-gene rearrangements are also found in some murine and human suppressor cell lines but others have been shown not to rearrange or express the beta-chain or alpha-chain genes. We previously established TS clones derived from lepromatous leprosy patients which carry the CD8 antigen and recognize antigen in the context of the major histocompatibility complex (MHC) class II molecules in vitro. We here report the characterization of additional MHC-restricted TS clones which rearrange TCR beta genes, express messenger RNA for the alpha and beta chains of the TCR and express clonally unique CD3-associated TCR alpha beta structures on their cell surface but do not express the gamma chain of the gamma delta TCR on the cell surface. We conclude that antigen recognition by at least some human CD8+ suppressor cells is likely to be mediated by TCR alpha beta heterodimers. 相似文献
753.
AIDS virus-specific cytotoxic T lymphocytes in lung disorders 总被引:6,自引:0,他引:6
F Plata B Autran L P Martins S Wain-Hobson M Rapha?l C Mayaud M Denis J M Guillon P Debré 《Nature》1987,328(6128):348-351
Human immunodeficiency virus (HIV) is implicated in the development of AIDS (acquired immune deficiency syndrome). HIV infection leads to the generation of HIV-specific thymus-derived (T) lymphocytes in humans and apes. We describe an experimental system permitting the quantitative and systematic analysis of HIV-specific cytotoxic T lymphocytes (CTL). Functional, HIV-specific CTL are obtained by broncho-alveolar lavage (BAL) from the lungs of seropositive patients with lymphocytic alveolitis. These alveolar CTL: (1) recognize and kill HIV-infected alveolar macrophages in vitro under autologous, but not heterologous, conditions; (2) correspond to standard CTL as they express the CD3 and CD8 surface markers, but not the CD4 marker; and (3) are restricted by class I HLA transplantation antigens in their cytotoxic activities. We propose the hypothesis that interactions between HIV-specific CTL and infected macrophages induce major inflammatory reactions in seropositive patients. 相似文献
754.
R A Dixon I S Sigal E Rands R B Register M R Candelore A D Blake C D Strader 《Nature》1987,326(6108):73-77
Recently the genes for several hormone receptors that interact with guanine nucleotide binding proteins (G proteins) have been cloned, including the hamster beta 2-adrenergic receptor (beta 2AR), a human beta AR, the turkey erythrocyte beta AR and the porcine muscarinic acetylcholine receptor (MAR). All these receptors share some amino-acid homology with rhodopsin, particularly in 7 hydrophobic stretches of residues that are believed to represent transmembrane helices. To determine whether differences in ligand specificity result from the divergence in the sequences of the hydrophilic regions of these receptors, we have expressed in mammalian cells genes for the wild-type hamster and human beta AR proteins, and a series of deletion mutant genes of the hamster beta 2AR. The pharmacology of the expressed receptors indicates that most of the hydrophilic residues are not directly involved in the binding of agonists or antagonists to the receptor. In addition, we have identified a mutant receptor that has high agonist affinity but does not couple to adenylate cyclase. 相似文献
755.
The role of clonal selection and somatic mutation in autoimmunity 总被引:25,自引:0,他引:25
M J Shlomchik A Marshak-Rothstein C B Wolfowicz T L Rothstein M G Weigert 《Nature》1987,328(6133):805-811
Polyclonal activation has been proposed as the reason that autoantibodies are produced during autoimmune disease. This model denies a role for specific antigen selection of B cells and predicts instead a multiclonal population of unmutated or randomly mutated autoantibodies. We have found that the genetic features and clonal composition of spontaneously derived immunoglobulin G (IgG) antiself-IgG (rheumatoid factor (RF] autoantibodies derived from the autoimmune MRL/lpr mouse strain are inconsistent with both the predictions of this model and the actual outcome of experimental polyclonal activation. Instead we have found that MRL/lpr RFs are oligoclonal or even monoclonal in origin. They harbour numerous somatic mutations which are distributed in a way that suggests immunoglobulin-receptor-dependent selection of these mutations. In this sense, the MRL/lpr RFs resemble antibodies elicited by exogenous antigens after secondary immunization. The parallels suggest that, like secondary immune responses, antigen stimulation is important in the generation of MRL/lpr RFs. 相似文献
756.
757.
Failure of familial Alzheimer's disease to segregate with the A4-amyloid gene in several European families 总被引:2,自引:0,他引:2
C Van Broeckhoven A M Genthe A Vandenberghe B Horsthemke H Backhovens P Raeymaekers W Van Hul A Wehnert J Gheuens P Cras 《Nature》1987,329(6135):153-155
The gene coding for the amyloid protein, a component of neuritic plaques found in brain tissue from patients with Alzheimer's disease, has been localized to chromosome 21, and neighbouring polymorphic DNA markers segregate with Alzheimer's disease in several large families. These data, and the association of Alzheimer's disease with Down's syndrome, suggest that overproduction of the amyloid protein, or production of an abnormal variant of the protein, may be the underlying pathological change causing Alzheimer's disease. We have identified a restriction fragment length polymorphism of the A4-amyloid gene, and find recombinants in two Alzheimer's disease families between Alzheimer's disease and the A4-amyloid locus. This demonstrates that the gene for plaque core A4-amyloid cannot be the locus of a defect causing Alzheimer's disease in these families. These data indicate that alterations in the plaque core amyloid gene cannot explain the molecular pathology for all cases of Alzheimer's disease. 相似文献
758.
Mouse embryogenesis relies on the presence of both the maternal and the paternal genome for development to term. It has been proposed that specific modifications are imprinted onto the chromosomes during gametogenesis; these modifications are stably propagated, and their expression results in distinct and complementary contributions of the two parental genomes to the development of the embryo and the extraembryonic membranes. Genetic data further suggest that a substantial proportion of the genome could be subject to chromosomal imprinting, the molecular nature of which is unknown. We used random DNA insertions in transgenic mice to probe the genome for modified regions. The DNA methylation patterns of transgenic alleles were compared after transmission from mother or father in seven mouse strains carrying autosomal insertions of the same transgenic marker. One of these loci showed a clear difference in DNA methylation specific for its parental origin, with the paternally inherited copy being relatively undermethylated. This difference was observed in embryos on day 10 of gestation, but not in their extraembryonic membranes. Moreover, the methylation pattern was faithfully reversed upon each germline transmission to the opposite sex. Our findings provide evidence for heritable molecular differences between maternally and paternally derived alleles on mouse chromosomes. 相似文献
759.
Characterization and molecular cloning of a bovine lentivirus related to human immunodeficiency virus 总被引:8,自引:0,他引:8
M A Gonda M J Braun S G Carter T A Kost J W Bess L O Arthur M J Van der Maaten 《Nature》1987,330(6146):388-391
760.
Neurons in the visual cortex typically respond selectively to the orientation, and velocity and direction of movement, of moving-bar stimuli. These responses are generally thought to provide information about the orientation and position of lines and edges in the visual field. Some cells are also endstopped, that is selective for bars of specific lengths. Hubel and Wiesel first observed that endstopped hypercomplex cells could respond to curved stimuli and suggested they might be involved in detection of curvature, but the exact relationship between endstopping and curvature has never been determined. We present here a mathematical model relating endstopping to curvature in which the difference in response of two simple cells gives rise to endstopping and varies in proportion to curvature. We also provide physiological evidence that endstopped cells in area 17 of the cat visual cortex are selective for curvature, whereas non-endstopped cells are not, and that some are selective for the sign of curvature. The prevailing view of edge and curve determination is that orientations are selected locally by the class of simple cortical cells and then integrated to form global curves. We have developed a computational theory of orientation selection which shows that measurements of orientation obtained by simple cells are not sufficient because there will be strong, incorrect responses from cells whose receptive fields (RFs) span distinct curves (Fig. 1). If estimates of curvature are available, however, these inappropriate responses can be eliminated. Curvature provides the key to structuring the network that underlies our theory and distinguishes it from previous lateral inhibition schemes. 相似文献