全文获取类型
收费全文 | 44457篇 |
免费 | 124篇 |
国内免费 | 194篇 |
专业分类
系统科学 | 350篇 |
丛书文集 | 920篇 |
教育与普及 | 85篇 |
理论与方法论 | 153篇 |
现状及发展 | 20464篇 |
研究方法 | 1654篇 |
综合类 | 20444篇 |
自然研究 | 705篇 |
出版年
2013年 | 343篇 |
2012年 | 560篇 |
2011年 | 1280篇 |
2010年 | 233篇 |
2008年 | 719篇 |
2007年 | 799篇 |
2006年 | 819篇 |
2005年 | 781篇 |
2004年 | 792篇 |
2003年 | 759篇 |
2002年 | 698篇 |
2001年 | 1311篇 |
2000年 | 1249篇 |
1999年 | 813篇 |
1992年 | 803篇 |
1991年 | 635篇 |
1990年 | 719篇 |
1989年 | 681篇 |
1988年 | 676篇 |
1987年 | 751篇 |
1986年 | 691篇 |
1985年 | 896篇 |
1984年 | 700篇 |
1983年 | 577篇 |
1982年 | 500篇 |
1981年 | 543篇 |
1980年 | 700篇 |
1979年 | 1382篇 |
1978年 | 1175篇 |
1977年 | 1162篇 |
1976年 | 941篇 |
1975年 | 993篇 |
1974年 | 1332篇 |
1973年 | 1177篇 |
1972年 | 1225篇 |
1971年 | 1391篇 |
1970年 | 1786篇 |
1969年 | 1352篇 |
1968年 | 1327篇 |
1967年 | 1305篇 |
1966年 | 1137篇 |
1965年 | 816篇 |
1964年 | 250篇 |
1959年 | 467篇 |
1958年 | 769篇 |
1957年 | 547篇 |
1956年 | 487篇 |
1955年 | 439篇 |
1954年 | 468篇 |
1948年 | 314篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
791.
Beside its role as a neurotransmitter in the central nervous system, serotonin appears to be a central physiologic mediator
of many gastrointestinal (GI) functions and a mediator of the brain-gut connection. By acting directly and via modulation
of the enteric nervous system, serotonin has numerous effects on the GI tract. The main gut disturbances in which serotonin
is involved are acute chemotherapy-induced nausea and vomiting, carcinoid syndrome and irritable bowel syndrome. Serotonin
also has mitogenic properties. Platelet-derived serotonin is involved in liver regeneration after partial hepatectomy. In
diseased liver, serotonin may play a crucial role in the progression of hepatic fibrosis and the pathogenesis of steatohepatitis.
Better understanding of the role of the serotonin receptor subtypes and serotonin mechanisms of action in the liver and gut
may open new therapeutic strategies in hepato-gastrointestinal diseases.
Received 15 August 2007; received after revision 1 November 2007; accepted 5 November 2007 相似文献
792.
Cajal bodies (CBs) and Gems are nuclear domains that contain factors responsible for spliceosomal small nuclear ribonucleoprotein
(snRNP) biogenesis. The marker protein for CBs is coilin. In addition to snRNPs, coilin and other factors, canonical CBs contain
the survivor of motor neuron protein (SMN). SMN can also localize to Gems. Considering the important role that coilin plays
in the formation and composition of CBs, we tested the splicing efficiency of several cell lines that vary in regards to coilin
level and modification using an artificial reporter substrate. We found that cells with both hypomethylated coilin and Gems
are more efficient at reporter splicing compared to cells in which SMN localizes to CBs. In contrast, coilin reduction, which
induces Gem formation, decreases cell proliferation and artificial reporter splicing. These findings demonstrate that coilin
modifications or levels impact artificial reporter splicing, possibly by influencing snRNP biogenesis.
Received 26 December 2007; received after revision 5 February 2008; accepted 7 February 2008 相似文献
793.
Hochrainer K Kroismayr R Baranyi U Binder BR Lipp J 《Cellular and molecular life sciences : CMLS》2008,65(13):2105-2117
Small HERC proteins are defined by the presence of one RCC1-like domain and a HECT domain. Having evolved out of one common ancestor, the four members of the family exhibit a high degree of homology in genomic organization and amino acid sequence, thus it seems possible that they might accomplish similar functions. Here we show that small HERC proteins interact with each other and localize to the same cellular structures, which we identify as late endosomes and lysosomes. We demonstrate interaction of HERC3 with the ubiquitin-like proteins hPLIC-1 and hPLIC-2 and we establish interaction of HERC5 with the metastasis suppressor Nm23B. While hPLIC proteins are not ubiquitinated by HERC3, HERC5 plays an important role in ubiquitination of Nm23B. In summary, although small HERC proteins are highly homologous showing the same subcellular distribution, they undergo different molecular interactions. 相似文献
794.
795.
The potential effects of synthetic unmethylated oligodeoxynucleotides (ODN) containing CpG motifs, mimicking bacterial DNA, has never been evaluated on the immune response in the teleost fish gilthead seabream (Sparus aurata), the most important fish species in Mediterranean aquaculture. First, binding and competition studies have demonstrated that binding is saturated and promiscuous, suggesting the participation of several receptors. Moreover, leucocyte cytotoxic (NCC) activity, production of ROIs (reactive oxygen intermediates), and expression of immune-relevant genes was greatly primed by ODNs. Focusing on the mechanism, the TLR9 gene is widely distributed in seabream tissues and differently regulated in vitro by several stimuli. Moreover, and for the first time in fish, TLR9 mRNA has been detected in lymphocytes as the main cell-source. To conclude, ODNs containing GACGTT, GTCGTT (optimal for mouse and human, respectively) or AACGTT motifs are the most potent inducers of seabream immunity, whilst the involvement of TLR9 is under debate. 相似文献
796.
797.
Scott RH Douglas J Baskcomb L Huxter N Barker K Hanks S Craft A Gerrard M Kohler JA Levitt GA Picton S Pizer B Ronghe MD Williams D;Factors Associated with Childhood Tumours 《Nature genetics》2008,40(11):1329-1334
Constitutional abnormalities at the imprinted 11p15 growth regulatory region cause syndromes characterized by disordered growth, some of which include a risk of Wilms tumor. We explored their possible contribution to nonsyndromic Wilms tumor and identified constitutional 11p15 abnormalities in genomic lymphocyte DNA from 13 of 437 individuals (3%) with sporadic Wilms tumor without features of growth disorders, including 12% of bilateral cases (P = 0.001) and in one familial Wilms tumor pedigree. No abnormality was detected in 220 controls (P = 0.006). Abnormalities identified included H19 DMR epimutations, uniparental disomy 11p15 and H19 DMR imprinting center mutations (one microinsertion and one microdeletion), thus identifying microinsertion as a new class of imprinting center mutation. Our data identify constitutional 11p15 defects as one of the most common known causes of Wilms tumor, provide mechanistic insights into imprinting disruption and reveal clinically important epigenotype-phenotype associations. The impact on clinical management dictates that constitutional 11p15 analysis should be considered in all individuals with Wilms tumor. 相似文献
798.
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
799.
Stacey SN Gudbjartsson DF Sulem P Bergthorsson JT Kumar R Thorleifsson G Sigurdsson A Jakobsdottir M Sigurgeirsson B Benediktsdottir KR Thorisdottir K Ragnarsson R Scherer D Rudnai P Gurzau E Koppova K Höiom V Botella-Estrada R Soriano V Juberías P Grasa M Carapeto FJ Tabuenca P Gilaberte Y Gudmundsson J Thorlacius S Helgason A Thorlacius T Jonasdottir A Blondal T Gudjonsson SA Jonsson GF Saemundsdottir J Kristjansson K Bjornsdottir G Sveinsdottir SG Mouy M Geller F Nagore E Mayordomo JI 《Nature genetics》2008,40(11):1313-1318
To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide SNP association study of 930 Icelanders with BCC and 33,117 controls. After analyzing 304,083 SNPs, we observed signals from loci at 1p36 and 1q42, and replicated these associations in additional sample sets from Iceland and Eastern Europe. Overall, the most significant signals were from rs7538876 on 1p36 (OR = 1.28, P = 4.4 x 10(-12)) and rs801114 on 1q42 (OR = 1.28, P = 5.9 x 10(-12)). The 1p36 locus contains the candidate genes PADI4, PADI6, RCC2 and ARHGEF10L, and the gene nearest to the 1q42 locus is the ras-homolog RHOU. Neither locus was associated with fair pigmentation traits that are known risk factors for BCC, and no risk was observed for melanoma. Approximately 1.6% of individuals of European ancestry are homozygous for both variants, and their estimated risk of BCC is 2.68 times that of noncarriers. 相似文献
800.
Olfactory receptors typically exhibit poor plasma membrane localization and functionality when heterologously expressed in
most cell types. It has therefore proven difficult to effectively study olfactory receptor pharmacology and signaling mechanisms
using traditional cell culture systems. Over the past few years, a variety of distinct proteins have been reported to interact
with olfactory receptors and facilitate olfactory receptor trafficking to the plasma membrane in heterologous cells. Advances
in this area have shed significant light on the fundamental factors governing the cell-specific control of olfactory receptor
trafficking. 相似文献