全文获取类型
收费全文 | 2285篇 |
免费 | 188篇 |
国内免费 | 1篇 |
出版年
2023年 | 9篇 |
2022年 | 17篇 |
2021年 | 26篇 |
2020年 | 18篇 |
2019年 | 26篇 |
2018年 | 26篇 |
2017年 | 24篇 |
2016年 | 48篇 |
2015年 | 101篇 |
2014年 | 116篇 |
2013年 | 145篇 |
2012年 | 171篇 |
2011年 | 181篇 |
2010年 | 132篇 |
2009年 | 97篇 |
2008年 | 127篇 |
2007年 | 146篇 |
2006年 | 123篇 |
2005年 | 116篇 |
2004年 | 85篇 |
2003年 | 101篇 |
2002年 | 76篇 |
2001年 | 34篇 |
2000年 | 33篇 |
1999年 | 23篇 |
1998年 | 19篇 |
1997年 | 18篇 |
1996年 | 17篇 |
1995年 | 24篇 |
1994年 | 21篇 |
1993年 | 13篇 |
1992年 | 21篇 |
1991年 | 24篇 |
1990年 | 17篇 |
1989年 | 23篇 |
1988年 | 16篇 |
1986年 | 12篇 |
1984年 | 27篇 |
1983年 | 11篇 |
1982年 | 13篇 |
1981年 | 11篇 |
1980年 | 9篇 |
1979年 | 11篇 |
1977年 | 13篇 |
1974年 | 9篇 |
1973年 | 9篇 |
1972年 | 9篇 |
1971年 | 10篇 |
1970年 | 8篇 |
1969年 | 15篇 |
排序方式: 共有2474条查询结果,搜索用时 20 毫秒
941.
Uniparental chromosome elimination at mitosis and interphase in wheat and pearl millet crosses involves micronucleus formation, progressive heterochromatinization, and DNA fragmentation 总被引:8,自引:0,他引:8
下载免费PDF全文
![点击此处可从《The Plant cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Gernand D Rutten T Varshney A Rubtsova M Prodanovic S Brüss C Kumlehn J Matzk F Houben A 《The Plant cell》2005,17(9):2431-2438
Complete uniparental chromosome elimination occurs in several interspecific hybrids of plants. We studied the mechanisms underlying selective elimination of the paternal chromosomes during the development of wheat (Triticum aestivum) x pearl millet (Pennisetum glaucum) hybrid embryos. All pearl millet chromosomes were eliminated in a random sequence between 6 and 23 d after pollination. Parental genomes were spatially separated within the hybrid nucleus, and pearl millet chromatin destined for elimination occupied peripheral interphase positions. Structural reorganization of the paternal chromosomes occurred, and mitotic behavior differed between the parental chromosomes. We provide evidence for a novel chromosome elimination pathway that involves the formation of nuclear extrusions during interphase in addition to postmitotically formed micronuclei. The chromatin structure of nuclei and micronuclei is different, and heterochromatinization and DNA fragmentation of micronucleated pearl millet chromatin is the final step during haploidization. 相似文献
942.
Rambach G Hagleitner M Mohsenipour I Lass-Flörl C Maier H Würzner R Dierich MP Speth C 《Microbes and infection / Institut Pasteur》2005,7(13):1285-1295
Dissemination of aspergillosis into the central nervous system is associated with nearly 100% mortality. To study the reasons for the antifungal immune failure we analyzed the efficacy of cerebral complement to combat the fungus Aspergillus. Incubation of Aspergillus in non-inflammatory cerebrospinal fluid (CSF) revealed that complement levels were sufficient to obtain a deposition on the surface, but opsonization was much weaker than in serum. Consequently complement deposition from normal CSF on fungal surface stimulated a very low phagocytic activity of microglia, granulocytes, monocytes and macrophages compared to stimulation by conidia opsonized in serum. Similarly, opsonization of Aspergillus by CSF was not sufficient to induce an oxidative burst in infiltrating granulocytes, whereas conidia opsonized in serum induced a clear respiratory signal. Thus, granulocytes were capable of considerably reducing the viability of serum-opsonized Aspergillus conidia, but not of conidia opsonized in CSF. The limited efficacy of antifungal attack by cerebral complement can be partly compensated by enhanced synthesis, leading to elevated complement concentrations in CSF derived from a patient with cerebral aspergillosis. This inflammatory CSF was able to induce (i) a higher complement deposition on the Aspergillus surface than non-inflammatory CSF, (ii) an accumulation of complement activation products and (iii) an increase in phagocytic and killing activity of infiltrating granulocytes. However, levels and efficacy of the serum-derived complement were not reached. These data indicate that low local complement synthesis and activation may represent a central reason for the insufficient antifungal defense in the brain and the high mortality rate of cerebral aspergillosis. 相似文献
943.
Farcasanu IC Mizunuma M Nishiyama F Miyakawa T 《Bioscience, biotechnology, and biochemistry》2005,69(12):2343-2348
Ni(2+) toxicity can be alleviated in yeast cells by exogenous L-histidine, but not by its enantiomer, D-histidine, nor by other natural L-amino acids tested. We studied the effect of L-histidine upon the accumulation and intracellular distribution of Ni(2+) and found that moderate L-histidine concentrations (less than or equal to those of Ni(2+)) increased cell tolerance without decreasing Ni(2+) accumulation. Although excess L-histidine appeared to lower Ni(2+) accumulation, the concomitant presence of Ni(2+) and L-histidine in the growth medium stimulated each other's uptake. 相似文献
944.
945.
Janig E Stumptner C Fuchsbichler A Denk H Zatloukal K 《European journal of cell biology》2005,84(2-3):329-339
Misfolded and aggregated proteins are a characteristic feature of a variety of chronic diseases. Examples include neurofibrillary tangles in Alzheimer disease, Lewy bodies in Parkinson disease and Mallory bodies (MBs) in chronic liver diseases, particularly alcoholic and non-alcoholic steatohepatitis (ASH and NASH). MB formation is at least in part the result of chronic oxidative cell stress in hepatocytes and can be induced in mice by long-term intoxication with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Proteomic analysis revealed that MBs consist of ubiquitinated keratins and the stress proteins Hsp70, Hsp25, and p62. Furthermore, marked overexpression of clusterin, which shares functional properties with small heat shock proteins, was identified by gene expression profiling of DDC-treated mice livers. To investigate whether clusterin has a function in the stress response to misfolded keratins, we performed transfection studies utilizing expression constructs encoding ubiquitin, p62, Hsp27, clusterin, keratin 8, and keratin 18. Ubiquitin was found in a strong and constant association with keratin aggregates, whereas binding of p62 to keratin was variable. Hsp27 did not colocalize with keratin aggregates under these experimental conditions. In contrast, clusterin associated with misfolded keratin only if its signal peptide was deleted and its secretion inhibited. This suggests that clusterin has ability to bind misfolded proteins, including keratins but its physiological function is restricted to the extracellular space. The extracellular localization of clusterin was underlined by immunohistochemical studies in Alzheimer disease brains, where clusterin was constantly found in association with amyloid plaques; in contrast, cytoplasmic inclusions such as neurofibrillary tangles as well as MBs in ASH were negative. Furthermore, we found clusterin in association with elastic fibers in the extracellular matrix in several chronic liver diseases, including ASH and alpha1-antitrypsin deficiency, implying a possible role of clusterin in liver fibrosis. 相似文献
946.
Lechel A Satyanarayana A Ju Z Plentz RR Schaetzlein S Rudolph C Wilkens L Wiemann SU Saretzki G Malek NP Manns MP Buer J Rudolph KL 《EMBO reports》2005,6(3):275-281
Telomere dysfunction induces two types of cellular response: cellular senescence and apoptosis. We analysed the extent to which the cellular level of telomere dysfunction and p53 gene status affect these cellular responses in mouse liver using the experimental system of TRF2 inhibition by a dominant-negative version of the protein (TRF2delta B delta M). We show that the level of telomere dysfunction correlates with the level of TRF2delta B delta M protein expression resulting in chromosomal fusions, aberrant mitotic figures and aneuploidy of liver cells. These alterations provoked p53-independent apoptosis, but a strictly p53-dependent senescence response in distinct populations of mouse liver cells depending on the cellular level of TRF2delta B delta M expression. Apoptosis was associated with higher expression of TRF2delta B delta M, whereas cellular senescence was associated with low levels of TRF2delta B delta M) expression. Our data provide experimental evidence that induction of senescence or apoptosis in vivo depends on the cellular level of telomere dysfunction and differentially on p53 gene function. 相似文献
947.
The novel protein KBP regulates mitochondria localization by interaction with a kinesin-like protein
Marcin?J?Wozniak Martina?Melzer Cornelia?Dorner Hans-Ulrich?Haring Reiner?LammersEmail author 《BMC cell biology》2005,6(1):35
Background
Members of the Kinesin-3 family of kinesin-like proteins mediate transport of axonal vesicles (KIF1A, KIF1Bβ), distribution of mitochondria (KIF1Bα) and anterograde Golgi to ER vesicle transport (KIF1C). Until now, little is known about the regulation of kinesin-like proteins. Several proteins interact with members of this protein family. Here we report on a novel, KIF1 binding protein (KBP) that was identified in yeast two-hybrid screens. 相似文献948.
Warrington KJ Kent PD Frye RL Lymp JF Kopecky SL Goronzy JJ Weyand CM 《Arthritis research & therapy》2005,7(5):R984-R991
The risk for cardiovascular (CV) disease is increased in rheumatoid arthritis (RA) but data on the burden of coronary atherosclerosis
in patients with RA are lacking. We conducted a retrospective case-control study of Olmsted County (MN, USA) residents with
RA and new-onset coronary artery disease (CAD) (n = 75) in comparison with age-and sex-matched controls with newly diagnosed CAD (n = 128). Angiographic scores of the first coronary angiogram and data on CV risk factors and CV events on follow-up were obtained
by chart abstraction. Patients with RA were more likely to have multi-vessel coronary involvement at first coronary angiogram
compared with controls (P = 0.002). Risk factors for CAD including diabetes, hypertension, hyperlipidemia, and smoking history were not significantly
different in the two cohorts. RA remained a significant risk factor for multi-vessel disease after adjustment for age, sex
and history of hyperlipidemia. The overall rate of CV events was similar in RA patients and controls; however, there was a
trend for increased CV death in patients with RA. In a nested cohort of patients with RA and CAD (n = 27), we measured levels of pro-inflammatory CD4+CD28null T cells by flow cytometry. These T cells have been previously implicated in the pathogenesis of CAD and RA. Indeed, CD4+CD28null T cells were significantly higher in patients with CAD and co-existent RA than in controls with stable angina (P = 0.001) and reached levels found in patients with acute coronary syndromes. Patients with RA are at increased risk for multi-vessel
CAD, although the risk of CV events was not increased in our study population. Expansion of CD4+CD28null T cells in these patients may contribute to the progression of atherosclerosis. 相似文献
949.
In rheumatoid arthritis, T cells, B cells, macrophages, and dendritic cells invade the synovial membranes, establishing complex microstructures that promote inflammatory/tissue destructive lesions. B cell involvement has been considered to be limited to autoantibody production. However, recent studies suggest that B cells support rheumatoid disease through other mechanisms. A critical element of rheumatoid synovitis is the process of ectopic lymphoid neogenesis, with highly efficient lymphoid architectures established in a nonlymphoid tissue site. Rheumatoid synovitis recapitulates the pathways of lymph node formation, and B cells play a key role in this process. Furthermore, studies of rheumatoid lesions implanted in immunodeficient mice suggest that T cell activation in synovitis is B cell dependent, indicating the role played by B cells in presenting antigens and providing survival signals. 相似文献
950.
Hermes R Hildebrandt TB Blottner S Walzer C Silinski S Patton ML Wibbelt G Schwarzenberger F Göritz F 《Theriogenology》2005,63(1):219-238
White rhinoceroses suffer from a low rate of reproduction in captivity. This study examines the role of male reproductive function as a contributing factor. We used ultrasonography to image accessory sex glands, testis and epididymis. Electroejaculation provided 36 ejaculates from 21 rhinoceroses. Based on the percentage of progressively motile spermatozoa, semen was categorized in three groups, high (I: >75%), intermediate (II: 50-70%) or low (III: <50%) quality. Only 52% of the males showed high semen quality. Ejaculates in the high motility category also had the highest proportion of morphologically intact spermatozoa. Both semen parameters, sperm motility and morphology, were found to positively correlate with size of the accessory sex glands. The semen category was associated with group size suggesting that the social status influenced functional reproductive parameters. Change of territorial status (n = 1) improved semen quality. Testicular fibrosis was characterized as a sign of reproductive ageing in all males older than 15 years of age (n = 13); although, this ageing process did not notably affect semen parameters. Furthermore, for the benefit of assisted-reproduction and genetic banking programs protocols for the storage of cooled semen and the cryopreservation of spermatozoa were designed using different cryodiluents. This report provides basic data for the evaluation of reproductive components and of breeding management in male rhinoceros. Our results indicate that low rate of reproduction in captivity can be attributed to reduced male reproductive fitness. Changes in management of white rhinoceroses may positively affect male reproductive function. 相似文献