全文获取类型
收费全文 | 7519篇 |
免费 | 654篇 |
国内免费 | 4篇 |
专业分类
8177篇 |
出版年
2023年 | 58篇 |
2022年 | 142篇 |
2021年 | 273篇 |
2020年 | 147篇 |
2019年 | 176篇 |
2018年 | 199篇 |
2017年 | 160篇 |
2016年 | 335篇 |
2015年 | 509篇 |
2014年 | 521篇 |
2013年 | 532篇 |
2012年 | 754篇 |
2011年 | 645篇 |
2010年 | 375篇 |
2009年 | 363篇 |
2008年 | 489篇 |
2007年 | 417篇 |
2006年 | 375篇 |
2005年 | 287篇 |
2004年 | 288篇 |
2003年 | 262篇 |
2002年 | 238篇 |
2001年 | 52篇 |
2000年 | 29篇 |
1999年 | 38篇 |
1998年 | 60篇 |
1997年 | 29篇 |
1996年 | 22篇 |
1995年 | 27篇 |
1994年 | 23篇 |
1993年 | 27篇 |
1992年 | 23篇 |
1991年 | 19篇 |
1990年 | 14篇 |
1989年 | 21篇 |
1988年 | 12篇 |
1987年 | 9篇 |
1986年 | 10篇 |
1985年 | 12篇 |
1984年 | 15篇 |
1983年 | 24篇 |
1982年 | 8篇 |
1981年 | 16篇 |
1980年 | 13篇 |
1979年 | 11篇 |
1978年 | 15篇 |
1977年 | 10篇 |
1976年 | 9篇 |
1975年 | 9篇 |
1974年 | 8篇 |
排序方式: 共有8177条查询结果,搜索用时 0 毫秒
51.
Summary DBA/2 mice inoculated with either cells from the syngeneic P815 tumor or tumor cell membrane extracts develop T suppressor cells which suppress the in vitro generation of cytotoxic T lymphocytes with specificity for the tumor. A soluble suppressor factor with similar properties can be isolated from suppressor cell-enriched populations. It can be highly purified by appropriate immunoadsorption. Antisera to this suppressor factor raised in either DBA/2 or C57BL/6 mice can specifically absorb out suppressor factor and eliminate suppressor cells in the presence of complement. The in vivo effects of these antisera were tested for their ability to modulate the growth of P815 tumors in DBA/2 mice. It was found that the antiserum raised in syngeneic (DBA/2) but not allogeneic (C57BL/6) mice was able to significantly slow the rate of tumor growth and to prolong survival in treated mice. The antiserum was effective in this way only if it was administered early in the course of tumor growth. It was shown that this effect was not attributable to the presence in the serum of antibodies directed to antigens present on P815 cells, and it therefore appears to be due to interference with the function of T suppressor cells arising early in the immune response to the tumor cells. 相似文献
52.
P.J. Gardiner Julia L. Copas C. Schneider H.O.J. Collier 《Prostaglandins & other lipid mediators》1980,19(3):349-370
2-Decarboxy 2-hydroxymethyl prostaglandin E1 (TR4161) relaxed isolated guinea-pig trachea with about double and relaxed human isolated bronchial muscle with about one half the potency of PGE1. In conscious restrained cats an aerosol of TR4161 was about 100–1000 times less active than PGE1 in inducing tracheobronchial irritation. When given intravenously or by aerosol to the anaesthetised spontaneously breathing guinea-pig, TR4161 was approximately equipotent with PGE1 in inhibiting histamine-induced bronchoconstriction and in reducing basal inherent tone. The onset and duration of the bronchodilator effects of TR4161 administered intravenously, however, were significantly longer than those of PGE1. In conscious guinea-pigs, TR4161 by aerosol was approximately three times more potent than PGE1 in preventing histamine-induced convulsions, whereas only TR4161 was active in this test system when the test drugs were administered orally. These observations indicate that TR4161 might be therapeutically useful as a non-irritant prostaglandin bronchodilator in conditions of airway obstruction. 相似文献
53.
Julia Bell-Quint Trudy Forte Paul Graham 《Biochemical and biophysical research communications》1981,99(2):700-706
Cultured rat hepatocytes were used to demonstrate that the liver can synthesize two forms of apolipoprotein B. Separation of apolipoprotein B by disc gel electrophoresis indicated that hepatocyte low density lipoprotein contains predominantly apolipoprotein B with an apparent molecular weight of 345,000 ± 5,055. In contrast, the major apolipoprotein B component of hepatocyte very low density lipoprotein is a variant form with a molecular weight of 242,000 ± 2,720. Hepatocyte high density lipoprotein, unlike plasma HDL, also contains apolipoprotein B with an apparent molecular weight of 244,000 ± 2,742. Incorporation of [3H] leucine into hepatocyte apolipoprotein B components suggested de novo synthesis. 相似文献
54.
55.
56.
A low molecular weight fraction from chitinase digested cell walls ofT. mentagrophytes containing both polysaccharide and peptide moieties was found to have immunological reactivity at both the cellular and humoral level. This fraction (UM2(a)) was further degraded by treatment with either a combination of pronase and carboxypeptidase A or with trypsin. Peptides were separated from the carbohydrate-rich fraction by ultrafiltration. The carbohydrate-rich fraction retained the ability to induce both immediate and delayed skin reactions in sensitized guinea pigs and to stimulate the proliferation of sensitized lymphocytesin vitro. The peptide moieties retained reactivity in that they caused delayed reactions and lymphocyte proliferation but were unable to induce immediate or Arthus reactions in sensitized animals. Tryptic peptides from UM2(a) were purified by ion exchange chromatography. A high proportion of these peptides demonstrated immunological activity at both the cellular and humoral level since they were capable of inducing delayed reactions and/or lymphocyte transformation, as well as being capable of blocking the complement fixation reaction between UM2 (a) and specific antiserum.This work was supported by grant number 6411 from the Medical Research Council of Canada.A. Kh. Al-Rammahy was supported by a scholarship from the Ministry of High Education, Iraq. 相似文献
57.
Dusanka Milenkovic Adrin Sanz-Moreno Julia Calzada-Wack Birgit Rathkolb Oana Veronica Amarie Raffaele Gerlini Antonio Aguilar-Pimentel Jelena Misic Marie-Lune Simard Eckhard Wolf Helmut Fuchs Valerie Gailus-Durner Martin Hrab de Angelis Nils-Gran Larsson 《PLoS genetics》2022,18(5)
Mitochondrial DNA (mtDNA) maintenance disorders are caused by mutations in ubiquitously expressed nuclear genes and lead to syndromes with variable disease severity and tissue-specific phenotypes. Loss of function mutations in the gene encoding the mitochondrial genome and maintenance exonuclease 1 (MGME1) result in deletions and depletion of mtDNA leading to adult-onset multisystem mitochondrial disease in humans. To better understand the in vivo function of MGME1 and the associated disease pathophysiology, we characterized a Mgme1 mouse knockout model by extensive phenotyping of ageing knockout animals. We show that loss of MGME1 leads to de novo formation of linear deleted mtDNA fragments that are constantly made and degraded. These findings contradict previous proposal that MGME1 is essential for degradation of linear mtDNA fragments and instead support a model where MGME1 has a critical role in completion of mtDNA replication. We report that Mgme1 knockout mice develop a dramatic phenotype as they age and display progressive weight loss, cataract and retinopathy. Surprisingly, aged animals also develop kidney inflammation, glomerular changes and severe chronic progressive nephropathy, consistent with nephrotic syndrome. These findings link the faulty mtDNA synthesis to severe inflammatory disease and thus show that defective mtDNA replication can trigger an immune response that causes age-associated progressive pathology in the kidney. 相似文献
58.
Julia Grube Marius Maximilian Woitok Antje Mohs Stephanie Erschfeld Celina Lynen Christian Trautwein Tobias Otto 《Cell death & disease》2022,13(8)
Ferroptosis is a novel type of programmed cell death that differs from apoptosis in that it involves iron-dependent peroxidation of membrane phospholipids. Its role in a variety of human disorders, including cancer has been hypothesized in recent years. While it may function as an endogenous tumor suppressor in a variety of cancers, its role during initiation and progression of liver cancer, particularly hepatocellular carcinoma (HCC), is yet unknown. Because HCC is most commonly found in chronically injured livers, we utilized two well-established mouse models of chronic injury-dependent HCC formation: Treatment with streptozotocin and high-fat diet as metabolic injury model, as well as treatment with diethylnitrosamine and carbon tetrachloride as toxic injury model. We used mice with hepatocyte-specific deletion of Acsl4, a key mediator of ferroptosis, to explore the significance of ferroptotic cell death in hepatocytes, the cell type of origin for HCC. Surprisingly, preventing ferroptotic cell death in hepatocytes by deleting Acsl4 does not increase the formation of HCC. Furthermore, Acsl4-deficient livers display less fibrosis and proliferation, especially in the HCC model of toxic damage. Intriguingly, in this model, the absence of ACSL4-dependent processes such as ferroptosis significantly slow down the growth of HCC. These findings suggest that during HCC formation in a chronically injured liver, ferroptotic cell death is not an endogenous tumor-suppressive mechanism. Instead, we find that ACSL4-dependent processes have an unanticipated cancer-promoting effect during HCC formation, which is most likely due to aggravated liver damage as demonstrated by increased hepatic fibrosis. Previous studies suggested that ferroptosis might have beneficial effects for patients during HCC therapy. As a result, during HCC progression and therapy, ferroptosis may have both cancer-promoting and cancer-inhibitory effects, respectively.Subject terms: Cancer models, Cancer genetics, Cell death 相似文献
59.
Eric J. Hartman Beejan Asady Julia D. Romano Isabelle Coppens 《Molecular biology of the cell》2022,33(5)
After mammalian cell invasion, the parasite Toxoplasma multiplies in a self-made membrane-bound compartment, the parasitophorous vacuole (PV). We previously showed that Toxoplasma interacts with many host cell organelles, especially from recycling pathways, and sequestrates Rab11A and Rab11B vesicles into the PV. Here, we examine the specificity of host Rab11 vesicle interaction with the PV by focusing on the recruitment of subpopulations of Rab11 vesicles characterized by different effectors, for example, Rab11-family interacting roteins (FIPs) or Arf6. Our quantitative microscopic analysis illustrates the presence of intra-PV vesicles with FIPs from class I (FIP1C, FIP2, FIP5) and class II (FIP3, FIP4) but to various degrees. The intra-PV delivery of vesicles with class I, but not class II, FIPs is dependent on Rab11 binding. Cell depletion of Rab11A results in a significant decrease in intra-PV FIP5, but not FIP3 vesicles. Class II FIPs also bind to Arf6, and we observe vesicles associated with FIP3-Rab11A or FIP3-Arf6 complexes concomitantly within the PV. Abolishing FIP3 binding to both Rab11 and Arf6 reduces the number of intra-PV FIP3 vesicles. These data point to a selective process of mammalian Rab11 vesicle recognition and scavenging mediated by Toxoplasma, suggesting that specific parasite PV proteins may be involved in these processes. 相似文献
60.
Thao Vu Julia Wrobel Benjamin G. Bitler Erin L. Schenk Kimberly R. Jordan Debashis Ghosh 《PLoS computational biology》2022,18(6)
The tumor microenvironment (TME), which characterizes the tumor and its surroundings, plays a critical role in understanding cancer development and progression. Recent advances in imaging techniques enable researchers to study spatial structure of the TME at a single-cell level. Investigating spatial patterns and interactions of cell subtypes within the TME provides useful insights into how cells with different biological purposes behave, which may consequentially impact a subject’s clinical outcomes. We utilize a class of well-known spatial summary statistics, the K-function and its variants, to explore inter-cell dependence as a function of distances between cells. Using techniques from functional data analysis, we introduce an approach to model the association between these summary spatial functions and subject-level outcomes, while controlling for other clinical scalar predictors such as age and disease stage. In particular, we leverage the additive functional Cox regression model (AFCM) to study the nonlinear impact of spatial interaction between tumor and stromal cells on overall survival in patients with non-small cell lung cancer, using multiplex immunohistochemistry (mIHC) data. The applicability of our approach is further validated using a publicly available multiplexed ion beam imaging (MIBI) triple-negative breast cancer dataset. 相似文献