全文获取类型
收费全文 | 46073篇 |
免费 | 92篇 |
国内免费 | 119篇 |
专业分类
系统科学 | 355篇 |
丛书文集 | 1081篇 |
教育与普及 | 119篇 |
理论与方法论 | 244篇 |
现状及发展 | 20304篇 |
研究方法 | 1722篇 |
综合类 | 21759篇 |
自然研究 | 700篇 |
出版年
2013年 | 287篇 |
2012年 | 587篇 |
2011年 | 1320篇 |
2010年 | 257篇 |
2008年 | 749篇 |
2007年 | 786篇 |
2006年 | 850篇 |
2005年 | 830篇 |
2004年 | 779篇 |
2003年 | 833篇 |
2002年 | 756篇 |
2001年 | 1357篇 |
2000年 | 1238篇 |
1999年 | 804篇 |
1992年 | 804篇 |
1991年 | 677篇 |
1990年 | 720篇 |
1989年 | 669篇 |
1988年 | 692篇 |
1987年 | 716篇 |
1986年 | 691篇 |
1985年 | 856篇 |
1984年 | 701篇 |
1983年 | 590篇 |
1982年 | 494篇 |
1981年 | 511篇 |
1980年 | 666篇 |
1979年 | 1422篇 |
1978年 | 1213篇 |
1977年 | 1205篇 |
1976年 | 877篇 |
1975年 | 994篇 |
1974年 | 1369篇 |
1973年 | 1208篇 |
1972年 | 1221篇 |
1971年 | 1477篇 |
1970年 | 1944篇 |
1969年 | 1502篇 |
1968年 | 1369篇 |
1967年 | 1449篇 |
1966年 | 1254篇 |
1965年 | 908篇 |
1964年 | 243篇 |
1959年 | 571篇 |
1958年 | 850篇 |
1957年 | 668篇 |
1956年 | 572篇 |
1955年 | 503篇 |
1954年 | 561篇 |
1948年 | 334篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
81.
R. Poggioli A. V. Vergoni A. Bertolini 《Cellular and molecular life sciences : CMLS》1985,41(2):265-266
Summary Hydrochlorothiazide, acutely injected in rats, has a weak analgesic activity per se and potentiates and prolongs the antinociceptive effect of morphine.This work was supported in part by grants from Consiglio Nazionale delle Ricerche, and by Ministero della Pubblica Istruzione, Roma. 相似文献
82.
H R Brenner 《Nature》1985,317(6038):572-573
83.
Edouard T Montagner A Dance M Conte F Yart A Parfait B Tauber M Salles JP Raynal P 《Cellular and molecular life sciences : CMLS》2007,64(13):1585-1590
Activating and inactivating mutations of SHP-2 are responsible, respectively, for the Noonan (NS) and the LEOPARD (LS) syndromes.
Clinically, these developmental disorders overlap greatly, resulting in the apparent paradox of similar diseases caused by
mutations that oppositely influence SHP-2 phosphatase activity. While the mechanisms remain unclear, recent functional analysis
of SHP-2, along with the identification of other genes involved in NS and in other related syndromes (neurofibromatosis-1,
Costello and cardio-facio-cutaneous syndromes), strongly suggest that Ras/MAPK represents the major signaling pathway deregulated
by SHP-2 mutants. We discuss the idea that, with the exception of LS mutations that have been shown to exert a dominant negative
effect, all disease-causing mutations involved in Ras/MAPK-mediated signaling, including SHP-2, might lead to enhanced MAPK
activation. This suggests that a narrow range of MAPK signaling is required for appropriate development. We also discuss the
possibility that LS mutations may not simply exhibit dominant negative activity.
Received 30 November 2006; received after revision 8 February 2007; accepted 13 March 2007 相似文献
84.
Crnković-Mertens I Wagener N Semzow J Gröne EF Haferkamp A Hohenfellner M Butz K Hoppe-Seyler F 《Cellular and molecular life sciences : CMLS》2007,64(9):1137-1144
Cancer cells are typically characterized by apoptosis deficiency. In order to investigate a possible role for the anti-apoptotic
livin gene in renal cell cancer (RCC), we analyzed its expression in tumor tissue samples and in RCC-derived cell lines. In addition,
we studied the contribution of livin to the apoptotic resistance of RCC cells by RNA interference (RNAi). Livin gene expression was detected in a significant portion of RCC tumor tissue specimens (13/14, 92.9%) and tumor-derived cell
lines (12/15, 80.0%). Moreover, targeted inhibition of livin by RNAi markedly sensitized RCC cells towards proapoptotic stimuli, such as UV irradiation or the chemotherapeutic drugs
etoposide, 5-fluorouracil, and vinblastine. These effects were specific for livin expressing tumor cells. We conclude that livin can contribute significantly to the apoptosis resistance of RCC cells. Targeted inhibition of livin could represent a novel therapeutic strategy to increase the sensitivity of renal cancers towards pro-apoptotic agents.
Received 30 November 2006; received after revision 22 February 2007; accepted 20 March 2007 相似文献
85.
86.
Summary Traces of nor-adrenaline restore the vascular action of adrenaline altered in epinephrectomized dogs to the reaction of the normal animal. Therefore it is claimed that the adrenals discharge one or several substances into the blood stream, which are necessary for the usual peripheral vascular action of adrenaline. Further investigations are in progress. 相似文献
87.
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
88.
Péterfy M Ben-Zeev O Mao HZ Weissglas-Volkov D Aouizerat BE Pullinger CR Frost PH Kane JP Malloy MJ Reue K Pajukanta P Doolittle MH 《Nature genetics》2007,39(12):1483-1487
Hypertriglyceridemia is a hallmark of many disorders, including metabolic syndrome, diabetes, atherosclerosis and obesity. A well-known cause is the deficiency of lipoprotein lipase (LPL), a key enzyme in plasma triglyceride hydrolysis. Mice carrying the combined lipase deficiency (cld) mutation show severe hypertriglyceridemia owing to a decrease in the activity of LPL and a related enzyme, hepatic lipase (HL), caused by impaired maturation of nascent LPL and hepatic lipase polypeptides in the endoplasmic reticulum (ER). Here we identify the gene containing the cld mutation as Tmem112 and rename it Lmf1 (Lipase maturation factor 1). Lmf1 encodes a transmembrane protein with an evolutionarily conserved domain of unknown function that localizes to the ER. A human subject homozygous for a deleterious mutation in LMF1 also shows combined lipase deficiency with concomitant hypertriglyceridemia and associated disorders. Thus, through its profound effect on lipase activity, LMF1 emerges as an important candidate gene in hypertriglyceridemia. 相似文献
89.
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
90.
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