全文获取类型
收费全文 | 15168篇 |
免费 | 28篇 |
国内免费 | 47篇 |
专业分类
系统科学 | 65篇 |
丛书文集 | 181篇 |
教育与普及 | 32篇 |
理论与方法论 | 73篇 |
现状及发展 | 6182篇 |
研究方法 | 792篇 |
综合类 | 7633篇 |
自然研究 | 285篇 |
出版年
2013年 | 105篇 |
2012年 | 267篇 |
2011年 | 546篇 |
2010年 | 107篇 |
2008年 | 322篇 |
2007年 | 309篇 |
2006年 | 322篇 |
2005年 | 334篇 |
2004年 | 322篇 |
2003年 | 280篇 |
2002年 | 262篇 |
2001年 | 458篇 |
2000年 | 442篇 |
1999年 | 311篇 |
1992年 | 267篇 |
1991年 | 197篇 |
1990年 | 224篇 |
1989年 | 219篇 |
1988年 | 223篇 |
1987年 | 218篇 |
1986年 | 205篇 |
1985年 | 293篇 |
1984年 | 229篇 |
1983年 | 158篇 |
1982年 | 167篇 |
1981年 | 152篇 |
1980年 | 181篇 |
1979年 | 418篇 |
1978年 | 309篇 |
1977年 | 307篇 |
1976年 | 289篇 |
1975年 | 323篇 |
1974年 | 385篇 |
1973年 | 363篇 |
1972年 | 379篇 |
1971年 | 434篇 |
1970年 | 552篇 |
1969年 | 464篇 |
1968年 | 469篇 |
1967年 | 431篇 |
1966年 | 383篇 |
1965年 | 287篇 |
1964年 | 87篇 |
1959年 | 169篇 |
1958年 | 297篇 |
1957年 | 199篇 |
1956年 | 185篇 |
1955年 | 150篇 |
1954年 | 185篇 |
1948年 | 138篇 |
排序方式: 共有10000条查询结果,搜索用时 203 毫秒
471.
The X-linked form of the human disease dyskeratosis congenita (DKC) is caused by mutations in the gene encoding dyskerin. Sufferers have defects in highly regenerative tissues such as skin and bone marrow, chromosome instability and a predisposition to develop certain types of malignancy. Dyskerin is a putative pseudouridine synthase, and it has been suggested that DKC may be caused by a defect in ribosomal RNA processing. Here we show that dyskerin is associated not only with H/ACA small nucleolar RNAs, but also with human telomerase RNA, which contains an H/ACA RNA motif. Telomerase adds simple sequence repeats to chromosome ends using an internal region of its RNA as a template, and is required for the indefinite proliferation of primary human cells. We find that primary fibroblasts and lymphoblasts from DKC-affected males are not detectably deficient in conventional H/ACA small nucleolar RNA accumulation or function; however, DKC cells have a lower level of telomerase RNA, produce lower levels of telomerase activity and have shorter telomeres than matched normal cells. The pathology of DKC is consistent with compromised telomerase function leading to a defect in telomere maintenance, which may limit the proliferative capacity of human somatic cells in epithelia and blood. 相似文献
472.
Distribution of spatial and nonspatial information in dorsal hippocampus 总被引:10,自引:0,他引:10
The hippocampus in the mammalian brain is required for the encoding of current and the retention of past experience. Previous studies have shown that the hippocampus contains neurons that encode information required to perform spatial and nonspatial short-term memory tasks. A more detailed understanding of the functional anatomy of the hippocampus would provide important insight into how such encoding occurs. Here we show that hippocampal neurons in the rat are distributed anatomically in distinct segments along the length of the hippocampus. Each longitudinal segment contains clusters of neurons that become active when the animal performs a task with spatial attributes. Within these same segments are ordered arrangements of neurons that encode the nonspatial aspects of the task appropriate to those spatial features. Thus, anatomical segregation of spatial information, together with the interleaved representation of nonspatial information, represents a structural framework that may help to resolve conflicting views of hippocampal function. 相似文献
473.
474.
Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana 总被引:21,自引:0,他引:21
Lin X Kaul S Rounsley S Shea TP Benito MI Town CD Fujii CY Mason T Bowman CL Barnstead M Feldblyum TV Buell CR Ketchum KA Lee J Ronning CM Koo HL Moffat KS Cronin LA Shen M Pai G Van Aken S Umayam L Tallon LJ Gill JE Adams MD Carrera AJ Creasy TH Goodman HM Somerville CR Copenhaver GP Preuss D Nierman WC White O Eisen JA Salzberg SL Fraser CM Venter JC 《Nature》1999,402(6763):761-768
Arabidopsis thaliana (Arabidopsis) is unique among plant model organisms in having a small genome (130-140 Mb), excellent physical and genetic maps, and little repetitive DNA. Here we report the sequence of chromosome 2 from the Columbia ecotype in two gap-free assemblies (contigs) of 3.6 and 16 megabases (Mb). The latter represents the longest published stretch of uninterrupted DNA sequence assembled from any organism to date. Chromosome 2 represents 15% of the genome and encodes 4,037 genes, 49% of which have no predicted function. Roughly 250 tandem gene duplications were found in addition to large-scale duplications of about 0.5 and 4.5 Mb between chromosomes 2 and 1 and between chromosomes 2 and 4, respectively. Sequencing of nearly 2 Mb within the genetically defined centromere revealed a low density of recognizable genes, and a high density and diverse range of vestigial and presumably inactive mobile elements. More unexpected is what appears to be a recent insertion of a continuous stretch of 75% of the mitochondrial genome into chromosome 2. 相似文献
475.
A structural change in the kinesin motor protein that drives motility 总被引:34,自引:0,他引:34
Rice S Lin AW Safer D Hart CL Naber N Carragher BO Cain SM Pechatnikova E Wilson-Kubalek EM Whittaker M Pate E Cooke R Taylor EW Milligan RA Vale RD 《Nature》1999,402(6763):778-784
Kinesin motors power many motile processes by converting ATP energy into unidirectional motion along microtubules. The force-generating and enzymatic properties of conventional kinesin have been extensively studied; however, the structural basis of movement is unknown. Here we have detected and visualized a large conformational change of an approximately 15-amino-acid region (the neck linker) in kinesin using electron paramagnetic resonance, fluorescence resonance energy transfer, pre-steady state kinetics and cryo-electron microscopy. This region becomes immobilized and extended towards the microtubule 'plus' end when kinesin binds microtubules and ATP, and reverts to a more mobile conformation when gamma-phosphate is released after nucleotide hydrolysis. This conformational change explains both the direction of kinesin motion and processive movement by the kinesin dimer. 相似文献
476.
Bacterial suicide through stress 总被引:9,自引:0,他引:9
Outside of the laboratory, bacterial cells are constantly exposed to stressful conditions, and an ability to resist those
stresses is essential to their survival. However, the degree of stress required to bring about cell death varies with growth
phase, amongst other parameters. Exponential phase cells are significantly more sensitive to stress than stationary phase
ones, and a novel hypothesis has recently been advanced to explain this difference in sensitivity, the suicide response. Essentially,
the suicide response predicts that rapidly growing and respiring bacterial cells will suffer growth arrest when subjected
to relatively mild stresses, but their metabolism will continue: a burst of free-radical production results from this uncoupling
of growth from metabolism, and it is this free-radical burst that is lethal to the cells, rather than the stress per se. The
suicide response hypothesis unifies a variety of previously unrelated empirical observations, for instance induction of superoxide
dismutase by heat shock, alkyl-hydroperoxide reductase by osmotic shock and catalase by ethanol shock. The suicide response
also has major implications for current [food] processing methods.
Received 29 March 1999; received after revision 14 May 1999; accepted 17 May 1999 相似文献
477.
Apolipoprotein E (apoE) ɛ4 allele is a genetic risk factor for late-onset familial and sporadic Alzheimer’s disease (AD).
In the central nervous system, apoE is secreted mainly by astrocytes as a constituent of high-density lipoproteins. A recent
study using apoE knockout mice provided strong evidence that apoE promotes cerebral deposition of amyloid β protein (Aβ).
However, no clear explanation of the pathogenesis of apoE-induced AD has been provided. Here we discuss two possible mechanisms
by which apoE might enhance Aβ deposition. One is the intracellular pathway in which apoE is internalized by neurons and induces
lysosomal accumulation of Aβ and amyloidogenic APP (amyloid precursor protein) fragments, leading to neuronal death. The other
is the extracellular pathway in which apoE-containing lipoproteins are trapped by Aβ1–42 deposits mobilizing soluble Aβ peptides
and consequently enlarge amyloid plaques. These two mechanisms may operate at different stages of AD pathogenesis and suggest
a chaperone-like function for the apoE molecule.
Received 4 February 1999; received after revision 9 April 1999; accepted 23 April 1999 相似文献
478.
A population of ventral neural tube cells has recently been shown to migrate out of the hind brain neural tube via the vagus
nerve and contribute to the developing gastrointestinal tract. Since liver is also innervated by the vagus nerve, we sought
to determine if these cells also migrate into the liver. Ventral neural tube cells in the caudal hindbrain of chick embryos
were tagged with a replication-deficient retroviral vector containing the LacZ gene on embryonic day 2. Embryos were processed
for detection of labeled cells on embryonic day 5 and 11. Labeled cells were seen in the liver on both days and identified
as hepatocytes. Previously, it was believed that all hepatocytes develop from the gut endoderm. Results of the present study
show an additional source for the formation of liver cells.
Received 25 August 1998; received after revision 5 November 1998; accepted 5 November 1998 相似文献
479.
480.
Favatier F Jacquier-Sarlin MR Swierczewski E Polla BS 《Cellular and molecular life sciences : CMLS》1999,56(7-8):701-708
A bi-allelic polymorphism found in the regulatory region of the human heat shock (HS) protein (HSP) hsp70-1 gene, which comprises an A-->C transversion, 3 bp upstream of the HS element (HSE), has been associated with extended HLA haplotypes. In view of the chaperoning and protective functions of Hsp70, we investigated whether this hsp70-1 bi-allelic polymorphism could modulate the stress response, which may relate to enhanced resistance or susceptibility to certain diseases. We compared the basal and HS-induced HS factor (HSF)-binding activity of the two polymorphic HSEs, hsp70-1 mRNA accumulation and HSP expression in two human Epstein Barr virus (EBV)-transformed B cell lines typed for hsp70-1 promoter alleles. Our results suggest that hsp70-1 promoter polymorphism does not influence HSF-binding activity, hsp70 mRNA accumulation or synthesis in human EBV-transformed B cell lines. 相似文献