全文获取类型
收费全文 | 5200篇 |
免费 | 19篇 |
国内免费 | 20篇 |
专业分类
系统科学 | 11篇 |
丛书文集 | 18篇 |
教育与普及 | 4篇 |
理论与方法论 | 11篇 |
现状及发展 | 2322篇 |
研究方法 | 263篇 |
综合类 | 2577篇 |
自然研究 | 33篇 |
出版年
2013年 | 53篇 |
2012年 | 105篇 |
2011年 | 123篇 |
2010年 | 29篇 |
2008年 | 90篇 |
2007年 | 120篇 |
2006年 | 100篇 |
2005年 | 103篇 |
2004年 | 124篇 |
2003年 | 86篇 |
2002年 | 94篇 |
2001年 | 182篇 |
2000年 | 149篇 |
1999年 | 119篇 |
1992年 | 112篇 |
1991年 | 72篇 |
1990年 | 75篇 |
1989年 | 65篇 |
1988年 | 69篇 |
1987年 | 78篇 |
1986年 | 56篇 |
1985年 | 97篇 |
1984年 | 92篇 |
1983年 | 79篇 |
1982年 | 63篇 |
1981年 | 56篇 |
1980年 | 72篇 |
1979年 | 181篇 |
1978年 | 146篇 |
1977年 | 115篇 |
1976年 | 121篇 |
1975年 | 130篇 |
1974年 | 151篇 |
1973年 | 123篇 |
1972年 | 125篇 |
1971年 | 151篇 |
1970年 | 202篇 |
1969年 | 147篇 |
1968年 | 151篇 |
1967年 | 127篇 |
1966年 | 138篇 |
1965年 | 107篇 |
1964年 | 41篇 |
1959年 | 43篇 |
1958年 | 72篇 |
1957年 | 47篇 |
1956年 | 41篇 |
1955年 | 36篇 |
1954年 | 48篇 |
1948年 | 29篇 |
排序方式: 共有5239条查询结果,搜索用时 109 毫秒
101.
Shin JM Vagin O Munson K Kidd M Modlin IM Sachs G 《Cellular and molecular life sciences : CMLS》2008,65(2):264-281
Inhibition of gastric acid secretion is the mainstay of the treatment of gastroesophageal reflux disease and peptic ulceration;
therapies to inhibit acid are among the best-selling drugs worldwide. Highly effective agents targeting the histamine H2 receptor
were first identified in the 1970s. These were followed by the development of irreversible inhibitors of the parietal cell
hydrogen-potassium ATPase (the proton pump inhibitors) that inhibit acid secretion much more effectively. Reviewed here are
the chemistry, biological targets and pharmacology of these drugs, with reference to their current and evolving clinical utilities.
Future directions in the development of acid inhibitory drugs include modifications of current agents and the emergence of
a novel class of agents, the acid pump antagonists.
Received 30 May 2007; received after revision 15 August 2007; accepted 13 September 2007 相似文献
102.
Dolezel D Zdechovanova L Sauman I Hodkova M 《Cellular and molecular life sciences : CMLS》2008,65(6):964-969
Current models state that insect peripheral oscillators are directly responsive to light, while mammalian peripheral clock
genes are coordinated by a master clock in the brain via intermediate factors, possibly hormonal. We show that the expression
levels of two circadian clock genes, period (per) and Par Domain Protein 1 (Pdp1) in the peripheral tissue of an insect model species, the linden bug Pyrrhocoris apterus, are inversely affected by contrasting photoperiods. The effect of photoperiod on per and Pdp1 mRNA levels was found to be mediated by the corpus allatum, an endocrine gland producing juvenile hormone. Our results
provide the first experimental evidence for the effect of an endocrine gland on circadian clock gene expression in insects.
Received 31 October 2007; received after revision 7 January 2008; accepted 9 January 2008
D. Dolezel, L. Zdechovanova: These authors contributed equally to this work. 相似文献
103.
Leung JY Chapman JA Harris JA Hale D Chung RS West AK Chuah MI 《Cellular and molecular life sciences : CMLS》2008,65(17):2732-2739
Olfactory ensheathing cells (OECs) have been shown previously to express Toll-like receptors and to respond to bacteria by translocating nuclear factor-kappaB from the cytoplasm to the nucleus. In this study, we show that OECs extended significantly more pseudopodia when they were exposed to Escherichia coli than in the absence of bacteria (p=0.019). Co-immunoprecipitation showed that E. coli binding to OECs was mediated by Toll-like receptor 4. Lyso-Tracker, a fluorescent probe that accumulates selectively in lysosomes, and staining for type 1 lysosome-associated membrane proteins demonstrated that endocytosed FITC-conjugated E. coli were translocated to lysosomes. They appeared to be subsequently broken down, as shown by transmission electron microscopy. No obvious adherence to the membrane and less phagocytosis was observed when OECs were incubated with inert fluorescent microspheres. The ability of OECs to endocytose bacteria supports the notion that OECs play an innate immune function by protecting olfactory tissues from bacterial infection. 相似文献
104.
105.
Kao WH Klag MJ Meoni LA Reich D Berthier-Schaad Y Li M Coresh J Patterson N Tandon A Powe NR Fink NE Sadler JH Weir MR Abboud HE Adler SG Divers J Iyengar SK Freedman BI Kimmel PL Knowler WC Kohn OF Kramp K Leehey DJ Nicholas SB Pahl MV Schelling JR Sedor JR Thornley-Brown D Winkler CA Smith MW Parekh RS;Family Investigation of Nephropathy Diabetes Research Group 《Nature genetics》2008,40(10):1185-1192
As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 5.70) but not diabetic ESRD (lod = 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% CI = 0.39-0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans. 相似文献
106.
Arachiche A Badirou I Dachary-Prigent J Garcin I Geldwerth-Feniger D Kerbiriou-Nabias D 《Cellular and molecular life sciences : CMLS》2008,65(23):3861-3871
Rapid Ca2+-dependent phospholipid (PL) reorganization (scrambling) at the plasma membrane is a mechanism common to hematopoietic cells
exposing procoagulant phosphatidylserine (PS). The aim of this research was to determine whether activation of the extracellular
signal-regulated kinase (ERK) pathway was required for PL scrambling, based on a single report analyzing both responses induced
by Ca2+ ionophores in megakaryoblastic HEL cells. Ca2+ ionophore-stimulated ERK phosphorylation was induced in platelets without external Ca2+, whereas exogenous Ca2+ entry was crucial for ERK activation in Jurkat T cells. In both cells, membrane scrambling only occurred following Ca2+ entry and was not blocked by inhibiting ERK phosphorylation. Furthermore, ERK proteins are strongly phosphorylated in transformed
B lymphoblastic cell lines, which do not expose PS in their resting state. Overall, the data demonstrated that ERK activation
and membrane scrambling are independent mechanisms.
A. Arachiche, I. Badirou: These authors contributed equally to this work.
Received 18 June 2008; received after revision 24 September 2008; accepted 1 October 2008 相似文献
107.
Loos RJ Lindgren CM Li S Wheeler E Zhao JH Prokopenko I Inouye M Freathy RM Attwood AP Beckmann JS Berndt SI;Prostate Lung Colorectal Ovarian 《Nature genetics》2008,40(6):768-775
To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits. 相似文献
108.
Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes 总被引:1,自引:0,他引:1
Zeggini E Scott LJ Saxena R Voight BF Marchini JL Hu T de Bakker PI Abecasis GR Almgren P Andersen G Ardlie K Boström KB Bergman RN Bonnycastle LL Borch-Johnsen K Burtt NP Chen H Chines PS Daly MJ Deodhar P Ding CJ Doney AS Duren WL Elliott KS Erdos MR Frayling TM Freathy RM Gianniny L Grallert H Grarup N Groves CJ Guiducci C Hansen T Herder C Hitman GA Hughes TE Isomaa B Jackson AU Jørgensen T Kong A Kubalanza K Kuruvilla FG Kuusisto J Langenberg C Lango H Lauritzen T Li Y Lindgren CM 《Nature genetics》2008,40(5):638-645
Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D. 相似文献
109.
110.
Ehsan Rakhshani Xavier Pons Belén Lumbierres Jan Havelka Nicolás Pérez Hidalgo Željko Tomanović 《Journal of Natural History》2017,51(21-22):1237-1248
A long-term survey of tritrophic (plant–aphid–parasitoid) associations in the urban ecosystems of Lleida (Catalonia) and Paris (France) resulted in the detection of associations of two bamboo aphids, Takecallis arundinariae (Essig) and Takecallis taiwanus (Takahashi), respectively, with a new aphid parasitoid species. Trioxys remaudierei Starý & Rakhshani sp. nov. is described and illustrated as a unique parasitoid of Takecallis aphids outside the area of their origin. The new species is easily distinguishable from its congeners in having the ventral prongs of the abdomen fused over two-thirds of their length, then bifurcated towards the tip. The only morphologically similar species is Trioxys betulae (Marshall), which exhibits a clearly different prong shape (and has a different host range, Symydobius Mordvilko and Clethrobius Mordvilko). The new species is compared with allied taxa associated with bamboo aphids. The occurrence of Takecallis taiwanus on bamboo is recorded in France for the first time.
www.zoobank.org/urn:lsid:zoobank.org:pub:ED15BA16-E8A9-4CEA-BDA7-FBAB02FEB091 相似文献