全文获取类型
收费全文 | 15121篇 |
免费 | 46篇 |
国内免费 | 72篇 |
专业分类
系统科学 | 128篇 |
丛书文集 | 219篇 |
教育与普及 | 43篇 |
理论与方法论 | 143篇 |
现状及发展 | 7317篇 |
研究方法 | 756篇 |
综合类 | 6414篇 |
自然研究 | 219篇 |
出版年
2018年 | 95篇 |
2013年 | 160篇 |
2012年 | 302篇 |
2011年 | 497篇 |
2010年 | 144篇 |
2008年 | 296篇 |
2007年 | 311篇 |
2006年 | 338篇 |
2005年 | 357篇 |
2004年 | 322篇 |
2003年 | 345篇 |
2002年 | 379篇 |
2001年 | 450篇 |
2000年 | 398篇 |
1999年 | 269篇 |
1992年 | 205篇 |
1991年 | 170篇 |
1990年 | 189篇 |
1989年 | 185篇 |
1988年 | 193篇 |
1987年 | 198篇 |
1986年 | 202篇 |
1985年 | 262篇 |
1984年 | 177篇 |
1983年 | 161篇 |
1982年 | 136篇 |
1981年 | 141篇 |
1980年 | 194篇 |
1979年 | 471篇 |
1978年 | 360篇 |
1977年 | 408篇 |
1976年 | 261篇 |
1975年 | 286篇 |
1974年 | 439篇 |
1973年 | 378篇 |
1972年 | 407篇 |
1971年 | 407篇 |
1970年 | 516篇 |
1969年 | 464篇 |
1968年 | 438篇 |
1967年 | 439篇 |
1966年 | 389篇 |
1965年 | 278篇 |
1959年 | 124篇 |
1958年 | 228篇 |
1957年 | 181篇 |
1956年 | 163篇 |
1955年 | 139篇 |
1954年 | 144篇 |
1948年 | 113篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
931.
GEChendong O.Slaymaker T.F.Pedersen 《科学通报(英文版)》2003,48(21):2357-2361
Pb geochronology and sediment core profiles of organic carbon, total sulfur and organic carbon isotope (d 13C) values were used to reconstruct the local environ-mental history of the Shamei Lagoon, located in the Wan-quan River Estuary, eastern Hainan Island, China. Totalsulfur and d 13C values decreased upwards in the top 30 cm of a sediment core that spanned the last 200 years of deposi-tion. Total sulfur concentration and d 13C values respectively decreased upward from 1.92% to 0.36%, and -20.63?to -23.64? The C/S ratio in the 19th century and earlier was relatively stable in the range of 0.47—0.80, and there was a positive correlation between organic carbon and total sulfur. Since around 1900 AD, the C/S ratio increased rapidly to a maximum of 3.94, but no simple correlation was found be-tween organic carbon and total sulfur during this more re-cent period. These results indicated that before 1800 AD, the lagoon had a fully marine character, and the location of to-day抯 Wanquan River Estuary was an open embayment.From 1800 to 1900, the salinity of Shamei Lagoon decreased noticeably. The amount of seawater which could enter thelagoon decreased gradually as the Yudai spit grew. Today,seawater scarcely affects the lagoon; it is essentially a fresh-water basin. 相似文献
932.
933.
934.
Nitric oxide can inhibit apoptosis or switch it into necrosis 总被引:4,自引:0,他引:4
Melino G Catani MV Corazzari M Guerrieri P Bernassola F 《Cellular and molecular life sciences : CMLS》2000,57(4):612-622
Nitric oxide (NO) and its related molecules are important messengers that play central roles in pathophysiology. Redox modulation of thiol groups on protein cysteine residues by S-nitrosylation can modulate protein function. NO has emerged as a potent regulator of apoptosis in many cell types, either preventing cell death or driving an apoptotic response into a necrotic one. NO protects neuroblastoma cells from retinoid- and cisplatin-induced apoptosis, without significantly increasing necrotic cell damage. Nitrosylation of thiol groups of several critical factors may be important for cell survival. Indeed, S-nitrosylation of the active-site cysteine residue of apoptotic molecules, such as caspases and tissue transglutaminase, results in the inhibition of their catalytic activities and has important implications for the regulation of apoptosis by NO. On the other hand, NO is able to shift the anti-CD95- and ceramide-triggered apoptotic response of Jurkat T cells into necrotic cell death. In these apoptotic models, NO is therefore unable to solely inhibit cell death, indicating that it may act below the point of no return elicited by CD95-ligation and ceramide stimulation. 相似文献
935.
Transport of lipids from golgi to plasma membrane is defective in tangier disease patients and Abc1-deficient mice 总被引:25,自引:0,他引:25
Orsó E Broccardo C Kaminski WE Böttcher A Liebisch G Drobnik W Götz A Chambenoit O Diederich W Langmann T Spruss T Luciani MF Rothe G Lackner KJ Chimini G Schmitz G 《Nature genetics》2000,24(2):192-196
Mutations in the gene encoding ATP-binding cassette transporter 1 ( ABC1) have been reported in Tangier disease (TD), an autosomal recessive disorder that is characterized by almost complete absence of plasma high-density lipoprotein (HDL), deposition of cholesteryl esters in the reticulo-endothelial system (RES) and aberrant cellular lipid trafficking. We demonstrate here that mice with a targeted inactivation of Abc1 display morphologic abnormalities and perturbations in their lipoprotein metabolism concordant with TD. ABC1 is expressed on the plasma membrane and the Golgi complex, mediates apo-AI associated export of cholesterol and phospholipids from the cell, and is regulated by cholesterol flux. Structural and functional abnormalities in caveolar processing and the trans-Golgi secretory pathway of cells lacking functional ABC1 indicate that lipid export processes involving vesicular budding between the Golgi and the plasma membrane are severely disturbed. 相似文献
936.
937.
MLH3: a DNA mismatch repair gene associated with mammalian microsatellite instability 总被引:24,自引:0,他引:24
Lipkin SM Wang V Jacoby R Banerjee-Basu S Baxevanis AD Lynch HT Elliott RM Collins FS 《Nature genetics》2000,24(1):27-35
DNA mismatch repair is important because of its role in maintaining genomic integrity and its association with hereditary non-polyposis colon cancer (HNPCC). To identify new human mismatch repair proteins, we probed nuclear extracts with the conserved carboxy-terminal MLH1 interaction domain. Here we describe the cloning and complete genomic sequence of MLH3, which encodes a new DNA mismatch repair protein that interacts with MLH1. MLH3 is more similar to mismatch repair proteins from yeast, plants, worms and bacteria than to any known mammalian protein, suggesting that its conserved sequence may confer unique functions in mice and humans. Cells in culture stably expressing a dominant-negative MLH3 protein exhibit microsatellite instability. Mlh3 is highly expressed in gastrointestinal epithelium and physically maps to the mouse complex trait locus colon cancer susceptibility I (Ccs1). Although we were unable to identify a mutation in the protein-coding region of Mlh3 in the susceptible mouse strain, colon tumours from congenic Ccs1 mice exhibit microsatellite instability. Functional redundancy among Mlh3, Pms1 and Pms2 may explain why neither Pms1 nor Pms2 mutant mice develop colon cancer, and why PMS1 and PMS2 mutations are only rarely found in HNPCC families. 相似文献
938.
Ross DT Scherf U Eisen MB Perou CM Rees C Spellman P Iyer V Jeffrey SS Van de Rijn M Waltham M Pergamenschikov A Lee JC Lashkari D Shalon D Myers TG Weinstein JN Botstein D Brown PO 《Nature genetics》2000,24(3):227-235
We used cDNA microarrays to explore the variation in expression of approximately 8,000 unique genes among the 60 cell lines used in the National Cancer Institute's screen for anti-cancer drugs. Classification of the cell lines based solely on the observed patterns of gene expression revealed a correspondence to the ostensible origins of the tumours from which the cell lines were derived. The consistent relationship between the gene expression patterns and the tissue of origin allowed us to recognize outliers whose previous classification appeared incorrect. Specific features of the gene expression patterns appeared to be related to physiological properties of the cell lines, such as their doubling time in culture, drug metabolism or the interferon response. Comparison of gene expression patterns in the cell lines to those observed in normal breast tissue or in breast tumour specimens revealed features of the expression patterns in the tumours that had recognizable counterparts in specific cell lines, reflecting the tumour, stromal and inflammatory components of the tumour tissue. These results provided a novel molecular characterization of this important group of human cell lines and their relationships to tumours in vivo. 相似文献
939.
940.
Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome 总被引:19,自引:0,他引:19
Ménasché G Pastural E Feldmann J Certain S Ersoy F Dupuis S Wulffraat N Bianchi D Fischer A Le Deist F de Saint Basile G 《Nature genetics》2000,25(2):173-176
Griscelli syndrome (GS, MIM 214450), a rare, autosomal recessive disorder, results in pigmentary dilution of the skin and the hair, the presence of large clumps of pigment in hair shafts and an accumulation of melanosomes in melanocytes. Most patients also develop an uncontrolled T-lymphocyte and macrophage activation syndrome (known as haemophagocytic syndrome, HS), leading to death in the absence of bone-marrow transplantation. In contrast, early in life some GS patients show a severe neurological impairment without apparent immune abnormalities. We previously mapped the GS locus to chromosome 15q21 and found a mutation in a gene (MYO5A) encoding a molecular motor in two patients. Further linkage analysis suggested a second gene associated with GS was in the same chromosomal region. Homozygosity mapping in additional families narrowed the candidate region to a 3.1-cM interval between D15S1003 and D15S962. We detected mutations in RAB27A, which lies within this interval, in 16 patients with GS. Unlike MYO5A, the GTP-binding protein RAB27A appears to be involved in the control of the immune system, as all patients with RAB27A mutations, but none with the MYO5A mutation, developed HS. In addition, RAB27A-deficient T cells exhibited reduced cytotoxicity and cytolytic granule exocytosis, whereas MYO5A-defective T cells did not. RAB27A appears to be a key effector of cytotoxic granule exocytosis, a pathway essential for immune homeostasis. 相似文献