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801.
ZHANG XianPing MA YanWei GAO ZhaoShun YU ZhengGuang WANG DongLiang WATANABE K GUO JianDong 《科学通报(英文版)》2007,52(18):2477-2480
Nano-SiC doped MgB2 tapes were prepared by the in situ powder-in-tube method. Heat treatment was performed at 650℃ for 1 h. XRD data indicate that SiC particles had reacted with the MgB2 during sintering process. MgB2 core seemed to be denser after SiC doping, and the critical temperature was slightly depressed. The critical current density Jc of the SiC doped tapes was significantly enhanced in magnetic fields up to 14 T compared to the undoped ones. For the 5% SiC doped samples, Jc was in- creased by a factor of 32 at 4.2 K, 10 T. The enhancement of Jc-B properties in SiC doped MgB2 tapes is considered to be due to the enhancement of grain linkages and the introduction of effective flux pining centers. The substitution of B by C in MgB2 grains is thought to be the main reason for the improve- ment of the flux pinning ability in SiC doped MgB2 tapes. 相似文献
802.
Telomerase activation is a common feature of advanced human cancers and facilitates the malignant transformation of cultured human cells and in mice. These experimental observations are in accord with the presence of robust telomerase activity in more advanced stages of human colorectal carcinogenesis. However, the occurrence of colon carcinomas in telomerase RNA (Terc)-null, p53-mutant mice has revealed complex interactions between telomere dynamics, checkpoint responses and carcinogenesis. We therefore sought to determine whether telomere dysfunction exerts differential effects on cancer initiation versus progression of mouse and human intestinal neoplasia. In successive generations of ApcMin Terc-/- mice, progressive telomere dysfunction led to an increase in initiated lesions (microscopic adenomas), yet a significant decline in the multiplicity and size of macroscopic adenomas. That telomere dysfunction also contributes to human colorectal carcinogenesis is supported by the appearance of anaphase bridges (a correlate of telomere dysfunction) at the adenoma-early carcinoma transition, a transition recognized for marked chromosomal instability. Together, these data are consistent with a model in which telomere dysfunction promotes the chromosomal instability that drives early carcinogenesis, while telomerase activation restores genomic stability to a level permissive for tumor progression. We propose that early and transient telomere dysfunction is a major mechanism underlying chromosomal instability of human cancer. 相似文献
803.
Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18. 总被引:33,自引:0,他引:33
J Parkhill G Dougan K D James N R Thomson D Pickard J Wain C Churcher K L Mungall S D Bentley M T Holden M Sebaihia S Baker D Basham K Brooks T Chillingworth P Connerton A Cronin P Davis R M Davies L Dowd N White J Farrar T Feltwell N Hamlin A Haque T T Hien S Holroyd K Jagels A Krogh T S Larsen S Leather S Moule P O'Gaora C Parry M Quail K Rutherford M Simmonds J Skelton K Stevens S Whitehead B G Barrell 《Nature》2001,413(6858):848-852
Salmonella enterica serovar Typhi (S. typhi) is the aetiological agent of typhoid fever, a serious invasive bacterial disease of humans with an annual global burden of approximately 16 million cases, leading to 600,000 fatalities. Many S. enterica serovars actively invade the mucosal surface of the intestine but are normally contained in healthy individuals by the local immune defence mechanisms. However, S. typhi has evolved the ability to spread to the deeper tissues of humans, including liver, spleen and bone marrow. Here we have sequenced the 4,809,037-base pair (bp) genome of a S. typhi (CT18) that is resistant to multiple drugs, revealing the presence of hundreds of insertions and deletions compared with the Escherichia coli genome, ranging in size from single genes to large islands. Notably, the genome sequence identifies over two hundred pseudogenes, several corresponding to genes that are known to contribute to virulence in Salmonella typhimurium. This genetic degradation may contribute to the human-restricted host range for S. typhi. CT18 harbours a 218,150-bp multiple-drug-resistance incH1 plasmid (pHCM1), and a 106,516-bp cryptic plasmid (pHCM2), which shows recent common ancestry with a virulence plasmid of Yersinia pestis. 相似文献
804.
Tissue-specific and reversible RNA interference in transgenic mice 总被引:11,自引:0,他引:11
Dickins RA McJunkin K Hernando E Premsrirut PK Krizhanovsky V Burgess DJ Kim SY Cordon-Cardo C Zender L Hannon GJ Lowe SW 《Nature genetics》2007,39(7):914-921
Genetically engineered mice provide powerful tools for understanding mammalian gene function. These models traditionally rely on gene overexpression from transgenes or targeted, irreversible gene mutation. By adapting the tetracycline (tet)-responsive system previously used for gene overexpression, we have developed a simple transgenic system to reversibly control endogenous gene expression using RNA interference (RNAi) in mice. Transgenic mice harboring a tet-responsive RNA polymerase II promoter driving a microRNA-based short hairpin RNA targeting the tumor suppressor Trp53 reversibly express short hairpin RNA when crossed with existing mouse strains expressing general or tissue-specific 'tet-on' or 'tet-off' transactivators. Reversible Trp53 knockdown can be achieved in several tissues, and restoring Trp53 expression in lymphomas whose development is promoted by Trp53 knockdown leads to tumor regression. By leaving the target gene unaltered, this approach permits tissue-specific, reversible regulation of endogenous gene expression in vivo, with potential broad application in basic biology and drug target validation. 相似文献
805.
Fox DW Yost S Kulkarni SR Torii K Kato T Yamaoka H Sako M Harrison FA Sari R Price PA Berger E Soderberg AM Djorgovski SG Barth AJ Pravdo SH Frail DA Gal-Yam A Lipkin Y Mauch T Harrison C Buttery H 《Nature》2003,422(6929):284-286
Observations of the long-lived emission--or 'afterglow'--of long-duration gamma-ray bursts place them at cosmological distances, but the origin of these energetic explosions remains a mystery. Observations of optical emission contemporaneous with the burst of gamma-rays should provide insight into the details of the explosion, as well as into the structure of the surrounding environment. One bright optical flash was detected during a burst, but other efforts have produced negative results. Here we report the discovery of the optical counterpart of GRB021004 only 193 seconds after the event. The initial decline is unexpectedly slow and requires varying energy content in the gamma-ray burst blastwave over the course of the first hour. Further analysis of the X-ray and optical afterglow suggests additional energy variations over the first few days. 相似文献
806.
807.
Interval Time Series Analysis with an Application to the Sterling-Dollar Exchange Rate 总被引:2,自引:0,他引:2
Traditional econometrics has long employed "points" to measure time series data. In real life situations, however, it suffers the loss of volatility information, since many variables are bounded by intervals in a given period. To address this issue, this paper provides a new methodology for interval time series analysis. The concept of "interval stochastic process" is formally defined as a counterpart of "stochastic process" in point-based econometrics. The authors introduce the concepts of interval stationarity, interval statistics (including interval mean, interval variance, etc.) and propose an interval linear model to investigate the dynamic relationships between interval processes. A new interval-based optimization approach for estimation is proposed, and corresponding evaluation criteria are derived. To demonstrate that the new interval method provides valid results, an empirical example on the sterling-dollar exchange rate is presented. 相似文献
808.
Stomata form pores on leaf surfaces that regulate the uptake of CO2 for photosynthesis and the loss of water vapour during transpiration. An increase in the cytosolic concentration of free calcium ions ([Ca2+]cyt) is a common intermediate in many of the pathways leading to either opening or closure of the stomatal pore. This observation has prompted investigations into how specificity is controlled in calcium-based signalling systems in plants. One possible explanation is that each stimulus generates a unique increase in [Ca2+]cyt, or 'calcium signature', that dictates the outcome of the final response. It has been suggested that the key to generating a calcium signature, and hence to understanding how specificity is controlled, is the ability to access differentially the cellular machinery controlling calcium influx and release from internal stores. Here we report that sphingosine-1-phosphate is a new calcium-mobilizing molecule in plants. We show that after drought treatment sphingosine-1-phosphate levels increase, and we present evidence that this molecule is involved in the signal-transduction pathway linking the perception of abscisic acid to reductions in guard cell turgor. 相似文献
809.
In the vertebrate central nervous system (CNS), a cascade of signals that originates in the ectoderm adjacent to the neural tube is propagated by the roof plate to dorsalize the neural tube. Here we report that the phenotype of the spontaneous neurological mutant mouse dreher (dr) results from a failure of the roof plate to develop. Dorsalization of the neural tube is consequently affected: dorsal interneurons in the spinal cord and granule neurons in the cerebellar cortex are lost, and the dorsal vertebral neural arches fail to form. Positional cloning of dreher indicates that the LIM homeodomain protein, Lmx1a, is affected in three different alleles of dreher. Lmx1a is expressed in the roof plate along the neuraxis during development of the CNS. Thus, Lmx1a is required for development of the roof plate and, in turn, for specification of dorsal cell fates in the CNS and developing vertebrae. 相似文献
810.
Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population 总被引:1,自引:0,他引:1
Yang L Soonpaa MH Adler ED Roepke TK Kattman SJ Kennedy M Henckaerts E Bonham K Abbott GW Linden RM Field LJ Keller GM 《Nature》2008,453(7194):524-528
The functional heart is comprised of distinct mesoderm-derived lineages including cardiomyocytes, endothelial cells and vascular smooth muscle cells. Studies in the mouse embryo and the mouse embryonic stem cell differentiation model have provided evidence indicating that these three lineages develop from a common Flk-1(+) (kinase insert domain protein receptor, also known as Kdr) cardiovascular progenitor that represents one of the earliest stages in mesoderm specification to the cardiovascular lineages. To determine whether a comparable progenitor is present during human cardiogenesis, we analysed the development of the cardiovascular lineages in human embryonic stem cell differentiation cultures. Here we show that after induction with combinations of activin A, bone morphogenetic protein 4 (BMP4), basic fibroblast growth factor (bFGF, also known as FGF2), vascular endothelial growth factor (VEGF, also known as VEGFA) and dickkopf homolog 1 (DKK1) in serum-free media, human embryonic-stem-cell-derived embryoid bodies generate a KDR(low)/C-KIT(CD117)(neg) population that displays cardiac, endothelial and vascular smooth muscle potential in vitro and, after transplantation, in vivo. When plated in monolayer cultures, these KDR(low)/C-KIT(neg) cells differentiate to generate populations consisting of greater than 50% contracting cardiomyocytes. Populations derived from the KDR(low)/C-KIT(neg) fraction give rise to colonies that contain all three lineages when plated in methylcellulose cultures. Results from limiting dilution studies and cell-mixing experiments support the interpretation that these colonies are clones, indicating that they develop from a cardiovascular colony-forming cell. Together, these findings identify a human cardiovascular progenitor that defines one of the earliest stages of human cardiac development. 相似文献