全文获取类型
收费全文 | 1818篇 |
免费 | 118篇 |
专业分类
1936篇 |
出版年
2023年 | 8篇 |
2022年 | 13篇 |
2021年 | 37篇 |
2020年 | 15篇 |
2019年 | 42篇 |
2018年 | 44篇 |
2017年 | 28篇 |
2016年 | 41篇 |
2015年 | 80篇 |
2014年 | 110篇 |
2013年 | 129篇 |
2012年 | 135篇 |
2011年 | 150篇 |
2010年 | 91篇 |
2009年 | 87篇 |
2008年 | 118篇 |
2007年 | 113篇 |
2006年 | 107篇 |
2005年 | 109篇 |
2004年 | 107篇 |
2003年 | 79篇 |
2002年 | 67篇 |
2001年 | 15篇 |
2000年 | 13篇 |
1999年 | 14篇 |
1998年 | 17篇 |
1997年 | 12篇 |
1996年 | 10篇 |
1995年 | 16篇 |
1994年 | 14篇 |
1993年 | 9篇 |
1992年 | 10篇 |
1991年 | 7篇 |
1990年 | 5篇 |
1989年 | 7篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 11篇 |
1983年 | 4篇 |
1982年 | 8篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 6篇 |
1978年 | 5篇 |
1976年 | 2篇 |
1975年 | 4篇 |
1972年 | 2篇 |
1970年 | 2篇 |
排序方式: 共有1936条查询结果,搜索用时 9 毫秒
11.
Matthew Breen Gabriella Lindgren Matthew M. Binns Julianne Norman Zlaka Irvin Kevin Bell Kaj Sandberg Hans Ellegren 《Mammalian genome》1997,8(4):267-273
Twenty equine microsatellites were isolated from a genomic phage library, and their genetical and physical localization was
sought by linkage mapping and fluorescent in situ hybridization (FISH). Nineteen of the markers were found to be polymorphic
with, in most cases, heterozygosities exceeding 50%. The markers were mapped in a Swedish reference family for gene mapping,
comprising eight half-sib families from Standardbred and Icelandic horse sires. Segregation was analyzed against a set of
35 other markers typed in the pedigree. Thirteen of the microsatellites showed linkage to at least one other marker, with
a total of 21 markers being involved in these linkages. In parallel, 18 of the microsatellites could be assigned to their
chromosomal region by FISH. These assignments involved eight equine autosomes: ECA1, 2, 4, 6, 9, 10, 15, and 16. The genetical
and physical mappings revealed by this study represent a significant extension of the current knowledge of the equine genome
map.
Received: 24 September 1996 / Accepted: 1 December 1996 相似文献
12.
Glucose Transporter (GLUT-4) Is Targeted to Secretory Granules in Rat Atrial Cardiomyocytes 总被引:6,自引:2,他引:4 下载免费PDF全文
Jan W. Slot Gabriella Garruti Sally Martin Viola Oorschot George Posthuma Edward W. Kraegen Ross Laybutt Gatan Thibault David E. James 《The Journal of cell biology》1997,137(6):1243-1254
The insulin-responsive glucose transporter GLUT-4 is found in muscle and fat cells in the transGolgi reticulum (TGR) and in an intracellular tubulovesicular compartment, from where it undergoes insulindependent movement to the cell surface. To examine the relationship between these GLUT-4–containing compartments and the regulated secretory pathway we have localized GLUT-4 in atrial cardiomyocytes. This cell type secretes an antihypertensive hormone, referred to as the atrial natriuretic factor (ANF), in response to elevated blood pressure. We show that GLUT-4 is targeted in the atrial cell to the TGR and a tubulo-vesicular compartment, which is morphologically and functionally indistinguishable from the intracellular GLUT-4 compartment found in other types of myocytes and in fat cells, and in addition to the ANF secretory granules. Forming ANF granules are present throughout all Golgi cisternae but only become GLUT4 positive in the TGR. The inability of cyclohexamide treatment to effect the TGR localization of GLUT-4 indicates that GLUT-4 enters the ANF secretory granules at the TGR via the recycling pathway and not via the biosynthetic pathway. These data suggest that a large proportion of GLUT-4 must recycle via the TGR in insulin-sensitive cells. It will be important to determine if this is the pathway by which the insulin-regulatable tubulo-vesicular compartment is formed. 相似文献
13.
Maurizio Meta Marco Ponte Marina Guastella Claudia Semino Gabriella Pietra Giovanni Battista Ratto Giovanni Melioli 《Cancer immunology, immunotherapy : CII》1995,40(4):235-240
Despite the combined use of surgery and chemoradiotherapy, the poor prognosis of advanced non-smallcell lung cancer (NSCLC) requires the definition of new therapeutic approaches. The presence of T lymphocytes, with peculiar phenotypic, functional and molecular characteristics within the tumour, suggested the possible use of these cells, expanded in vitro, in protocols of adoptive immunotherapy. We have described how a population of oligoclonal T lymphocytes, derived from advanced NSCLC, can be expanded in vitro and has the capability of lysing autologous cancer cells. What is more important, we observed that patients with advanced NSCLC, treated with TIL expanded in vitro and recombinant interleukin-2, seemed to have a disease-free period longer than that of patients treated with conventional chemoradiotherapy. in an attempt to find new sources of specific lymphocytes for immunotherapy, we describe the analysis of the phenotypic, functional and molecular characteristics of T lymphocytes, derived from lymph nodes draining advanced NSCLC. In this paper we show that these cells, have restriction patterns of T cell receptor chain similar to those detectable in the population of infiltrating T lymphocytes. This finding suggests that T cells derived from draining lymph nodes of advanced NSCLC have peculiar characteristics and can be a suitable source of effector cells for protocols of adoptive immunotherapy in lung cancer treatment. 相似文献
14.
Walter Balduini Gabriella Lombardelli Guidubaldo Peruzzi Flaminio Cattabeni 《Neurochemical research》1995,20(10):1211-1216
Carbachol-, norepinephrine- and glutamate-stimulated phosphoinositide metabolism was investigated in the neonatal, young and adult cerebral cortex slices of rats prenatally treated with methylazoxymethanol (MAM) on gestational day 15 (GD15) or GD19. In rat offspring treated on GD15 there was a significant reduction in the accumulation of [3H]inositol phosphates induced by carbachol and a significant increase in the accumulation of [3H]inositol phosphates induced by norepinephrine on day 7, whereas no changes were observed at the other ages. No significant changes, on the other hand, were observed for glutamate-stimulated phosphoinositide metabolism in GD15 treated rats and for carbachol-, norepinephrine- and glutamate-stimulated phosphoinositide metabolism in animals treated on GD19 at any of the different ages evaluated. These results indicate that treatment with MAM on GD15, which results in a marked microencephaly, causes a marked alteration of muscarinic and 1-adrenergic receptor-stimulated phosphoinositide metabolism during brain development and that these alterations undergo adaptive changes in the adult brain. 相似文献
15.
Horse serum Cholinesterase hydrolyzes choline and p-nitrophenol esters at different rates. Deacylation and acylation seem to be the rate-limiting step for charged and uncharged substrates respectively. Activation energy is similar for the acetic, propionic, and butyric esters of thiocholine, but it is higher for p-nitrophenylpropionate. Inhibition by the tetramethyl-ammonium ion is competitive. Tetraethyl-, tetrapropyl-, and tetrabutyl-ammonium ions are mixed-type inhibitors. The pH studies demonstrated the existence of a residue, pK = 6.33, involved in catalysis. 相似文献
16.
17.
18.
Aquilano K Filomeni G Di Renzo L Vito Md Stefano Cd Salimei PS Ciriolo MR Marfè G 《Free radical research》2007,41(4):452-460
In this study, we found that production of both reactive oxygen (ROS) and nitrogen (RNS) species is a very early event related to treatment with hyperosmotic concentration of sorbitol. The production of nitric oxide (NO) was paralleled by the increase of the mRNA and protein level of the inducible form of the nitric oxide synthase (iNOS). ROS and RNS enhancement, process concomitant to the failure of mitochondrial trans-membrane potential (ΔΨ), was necessary for the induction of apoptosis as demonstrated by the protection against sorbitol-mediated toxicity observed after treatment with ROS scavengers or NOS inhibitors. The synergistic action of ROS and RNS was finally demonstrated by pre-treatment with rosmarinic acid that, by powerfully buffering both these species, prevents impairment of ΔΨ and cell death. Overall results suggest that the occurrence of apoptosis upon sorbitol treatment is an event mediated by oxidative/nitrosative stress rather than a canonical hyperosmotic shock. 相似文献
19.
Cascone T Morelli MP Morgillo F Kim WY Rodolico G Pepe S Tortora G Berrino L Lee HY Heymach JV Ciardiello F 《Journal of cellular physiology》2008,216(3):698-707
The proteasome plays a pivotal role in the turnover of regulatory transduction proteins induced by activated cell membrane growth factor receptors. The epidermal growth factor receptor (EGFR) pathway is crucial in the development and progression of human epithelial cancers. Proteasome inhibition may sensitize human cancer cell lines to EGFR inhibitors. We investigated the growth inhibitory and pro-apoptotic effects of the proteasome inhibitor bortezomib in combination with anti-EGFR drugs, such as gefitinib, vandetanib, and cetuximab in EGFR-expressing human cancer cell lines. Bortezomib determined dose-dependent growth inhibition in a nine cancer cell line panel (IC(50) values, range 6-42 nM). A significant synergistic growth inhibitory effect was observed with the combination of bortezomib and each EGFR inhibitor in all cell lines (combination index, CI, range 0.10-0.55), which was accompanied by a significant induction in apoptosis by the combined treatment with bortezomib, cetuximab and vandetanib. In HCT-116 colon cancer and A549 lung adenocarcinoma cells, bortezomib plus EGFR inhibitor treatment induced a more effective inhibition of EGFR-activated down-stream signals, including a marked suppression in activated, phosphorylated Akt (P-Akt). In contrast, overexpression of a constitutively active P-Akt protected A549 cells by cell growth inhibition and apoptosis following treatment with bortezomib and EGFR inhibitors. The combined treatment with bortezomib and EGFR inhibitors has a synergistic growth inhibitory and pro-apoptotic activity in different human cancer cells which possess a functional EGFR-dependent autocrine growth pathway through to a more efficient and sustained inhibition of Akt. 相似文献
20.