全文获取类型
收费全文 | 36954篇 |
免费 | 111篇 |
国内免费 | 212篇 |
专业分类
系统科学 | 193篇 |
丛书文集 | 517篇 |
教育与普及 | 64篇 |
理论与方法论 | 131篇 |
现状及发展 | 17506篇 |
研究方法 | 1509篇 |
综合类 | 16851篇 |
自然研究 | 506篇 |
出版年
2013年 | 295篇 |
2012年 | 526篇 |
2011年 | 1027篇 |
2010年 | 226篇 |
2008年 | 656篇 |
2007年 | 726篇 |
2006年 | 747篇 |
2005年 | 686篇 |
2004年 | 673篇 |
2003年 | 650篇 |
2002年 | 713篇 |
2001年 | 1177篇 |
2000年 | 1078篇 |
1999年 | 753篇 |
1992年 | 728篇 |
1991年 | 533篇 |
1990年 | 608篇 |
1989年 | 605篇 |
1988年 | 584篇 |
1987年 | 662篇 |
1986年 | 600篇 |
1985年 | 756篇 |
1984年 | 643篇 |
1983年 | 484篇 |
1982年 | 460篇 |
1981年 | 490篇 |
1980年 | 576篇 |
1979年 | 1185篇 |
1978年 | 1023篇 |
1977年 | 925篇 |
1976年 | 822篇 |
1975年 | 817篇 |
1974年 | 1042篇 |
1973年 | 929篇 |
1972年 | 955篇 |
1971年 | 1065篇 |
1970年 | 1372篇 |
1969年 | 1005篇 |
1968年 | 1067篇 |
1967年 | 1025篇 |
1966年 | 884篇 |
1965年 | 623篇 |
1964年 | 232篇 |
1959年 | 318篇 |
1958年 | 567篇 |
1957年 | 368篇 |
1956年 | 333篇 |
1955年 | 313篇 |
1954年 | 302篇 |
1948年 | 210篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
61.
62.
Sobacchi C Frattini A Guerrini MM Abinun M Pangrazio A Susani L Bredius R Mancini G Cant A Bishop N Grabowski P Del Fattore A Messina C Errigo G Coxon FP Scott DI Teti A Rogers MJ Vezzoni P Villa A Helfrich MH 《Nature genetics》2007,39(8):960-962
Autosomal recessive osteopetrosis is usually associated with normal or elevated numbers of nonfunctional osteoclasts. Here we report mutations in the gene encoding RANKL (receptor activator of nuclear factor-KB ligand) in six individuals with autosomal recessive osteopetrosis whose bone biopsy specimens lacked osteoclasts. These individuals did not show any obvious defects in immunological parameters and could not be cured by hematopoietic stem cell transplantation; however, exogenous RANKL induced formation of functional osteoclasts from their monocytes, suggesting that they could, theoretically, benefit from exogenous RANKL administration. 相似文献
63.
Kitamura T Kometani K Hashida H Matsunaga A Miyoshi H Hosogi H Aoki M Oshima M Hattori M Takabayashi A Minato N Taketo MM 《Nature genetics》2007,39(4):467-475
Inactivation of TGF-beta family signaling is implicated in colorectal tumor progression. Using cis-Apc(+/Delta716) Smad4(+/-) mutant mice (referred to as cis-Apc/Smad4), a model of invasive colorectal cancer in which TGF-beta family signaling is blocked, we show here that a new type of immature myeloid cell (iMC) is recruited from the bone marrow to the tumor invasion front. These CD34(+) iMCs express the matrix metalloproteinases MMP9 and MMP2 and the CC-chemokine receptor 1 (CCR1) and migrate toward the CCR1 ligand CCL9. In adenocarcinomas, expression of CCL9 is increased in the tumor epithelium. By deleting Ccr1 in the background of the cis-Apc/Smad4 mutant, we further show that lack of CCR1 prevents accumulation of CD34(+) iMCs at the invasion front and suppresses tumor invasion. These results indicate that loss of transforming growth factor-beta family signaling in tumor epithelium causes accumulation of iMCs that promote tumor invasion. 相似文献
64.
Rogaeva E Meng Y Lee JH Gu Y Kawarai T Zou F Katayama T Baldwin CT Cheng R Hasegawa H Chen F Shibata N Lunetta KL Pardossi-Piquard R Bohm C Wakutani Y Cupples LA Cuenco KT Green RC Pinessi L Rainero I Sorbi S Bruni A Duara R Friedland RP Inzelberg R Hampe W Bujo H Song YQ Andersen OM Willnow TE Graff-Radford N Petersen RC Dickson D Der SD Fraser PE Schmitt-Ulms G Younkin S Mayeux R Farrer LA St George-Hyslop P 《Nature genetics》2007,39(2):168-177
The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease. 相似文献
65.
Minagawa H Yoshida Y Kenmochi N Furuichi M Shimada J Kaneko H 《Cellular and molecular life sciences : CMLS》2007,64(1):77-81
Lactate oxidase is used in biosensors to measure the concentration of lactate in the blood and other body fluids. Increasing
the thermostability of lactate oxidase can significantly prolong the lifetime of these biosensors. We have previously obtained
a variant of lactate oxidase from Aerococcus viridans with two mutations (E160G/V198I) that is significantly more thermostable than the wild-type enzyme. Here we have attempted
to further improve the thermostability of E160G/V198I lactate oxidase using directed evolution. We made a mutant lactate oxidase
gene library by applying error-prone PCR and DNA shuffling, and screened for thermostable mutant lactate oxidase using a plate-based
assay. After three rounds of screening we obtained a thermostable mutant lactate oxidase, which has six mutations (E160G/V198I/G36S/T103S/A232S/F277Y).
The half-life of this lactate oxidase at 70 °C was about 2 times that of E160G/V198I and about 36 times that of the wild-type
enzyme. The amino acid mutation process suggests that the combined neutral mutations are important in protein evolution.
Received 15 September 2006; received after revision 21 October 2006; accepted 2 November 2006 相似文献
66.
Untangling the molecular nature of sperm-egg interactions is fundamental if we are to understand fertilization. These phenomena
have been studied for many years using biochemical approaches such as antibodies and ligands that interact with sperm or with
eggs and their vestments. However, when homologous genetic recombination techniques were applied, most of the phenotypic factors
of the gene-manipulated animals believed “essential” for fertilization were found to be dispensable. Of course, all biological
systems contain redundancies and compensatory mechanisms, but as a whole the old model of fertilization clearly requires significant
modification. In this review, we use the results of gene manipulation experiments in animals to propose the basis for a new
vision.
Received 26 January 2007; received after revision 7 March 2007; accepted 17 April 2007 相似文献
67.
Lanigan F O'Connor D Martin F Gallagher WM 《Cellular and molecular life sciences : CMLS》2007,64(24):3159-3184
During its lifetime, the mammary gland undergoes many phases of development and differentiation. Much of this occurs during
puberty, when the ductal epithelium expands by branching morphogenesis, invading the surrounding fat pad to form an organised
mammary tree. Throughout its existence, the epithelium will go through several cycles of proliferation and cell death during
pregnancy, lactation and involution. Many of the signalling mechanisms which control the initial invasion of the fat pad by
the epithelium, and regulate its continuing plasticity, can be harnessed or corrupted by tumour cells in order to support
their aberrant growth and progression towards invasion. This is true not just for the epithelial cells themselves but also
for cells in the surrounding microenvironment, including fibroblasts, macrophages and adipocytes. This review examines the
complex web of signalling and adhesion interactions controlling branching morphogenesis, and how their alteration can promote
malignancy. Current in vivo and in vitro mammary gland models are also discussed. (Part of a Multi-author Review) 相似文献
68.
1 Results The development of the concepts of nanotechnology has given an important impact on the design of new polymer based materials which are in most cases characterized by a multiphase morphology. When at least one phase has nanometric dimension(s) the system can be considered as a nanocomposite where the interface is not only determining for the adhesion but also may play a role in some bulk properties. Indeed in nanostructured multiphase solids the interface is significant as a bulk component. The... 相似文献
69.
1 Results Pyrimidinones (PMs) are a class of important heterocycles which have been well documented throughout the literature due to their biological importance. They exhibit a wide range of pharmaceutical and therapeutic properties[1].A rapid and efficient one-pot method for the synthesis of 4,6-diarylpyrimidin-2(1H)- ones and related heterocycles is described.The condensation of acetophenone derivatives,aldehydes and urea in the presence of sulfamic acid was employed to synthesize a variety of pyrimid... 相似文献
70.
A fast and accurate method based on FTIR is developed for determining the lignin content and its characteristic bands in alkali solutions. The work consisted of two main parts: 1) establishing a predictive model and 2) determination of the accuracy of the model. The model was derived by applying the partial least squares algorithm for multivariate analyses to a set of spectrum data obtained from selected IR absorption regions in the range of 1600 - 900 cm-1. The model was tested with spent liquors obtained from commercial pulp mills.The accuracy of the predictive model is extremely high suitable for commercial applications,particularly for monitoring the dynamic response of modern kraft pulping processes. 相似文献