全文获取类型
收费全文 | 5170篇 |
免费 | 476篇 |
出版年
2023年 | 6篇 |
2022年 | 41篇 |
2021年 | 77篇 |
2020年 | 42篇 |
2019年 | 74篇 |
2018年 | 77篇 |
2017年 | 76篇 |
2016年 | 140篇 |
2015年 | 236篇 |
2014年 | 285篇 |
2013年 | 339篇 |
2012年 | 400篇 |
2011年 | 357篇 |
2010年 | 250篇 |
2009年 | 249篇 |
2008年 | 326篇 |
2007年 | 314篇 |
2006年 | 332篇 |
2005年 | 331篇 |
2004年 | 308篇 |
2003年 | 241篇 |
2002年 | 248篇 |
2001年 | 68篇 |
2000年 | 47篇 |
1999年 | 57篇 |
1998年 | 83篇 |
1997年 | 44篇 |
1996年 | 40篇 |
1995年 | 37篇 |
1994年 | 46篇 |
1993年 | 44篇 |
1992年 | 36篇 |
1991年 | 31篇 |
1990年 | 51篇 |
1989年 | 30篇 |
1988年 | 28篇 |
1987年 | 19篇 |
1986年 | 20篇 |
1985年 | 27篇 |
1984年 | 24篇 |
1983年 | 15篇 |
1982年 | 15篇 |
1981年 | 16篇 |
1980年 | 20篇 |
1979年 | 10篇 |
1978年 | 18篇 |
1976年 | 14篇 |
1974年 | 6篇 |
1973年 | 7篇 |
1971年 | 7篇 |
排序方式: 共有5646条查询结果,搜索用时 15 毫秒
991.
992.
Omura T Kaneko M Okuma Y Orba Y Nagashima K Takahashi R Fujitani N Matsumura S Hata A Kubota K Murahashi K Uehara T Nomura Y 《Journal of neurochemistry》2006,99(6):1456-1469
It has been proposed that in autosomal recessive juvenile parkinsonism (AR-JP), a ubiquitin ligase (E3) Parkin, which is involved in endoplasmic reticulum-associated degradation (ERAD), lacks E3 activity. The resulting accumulation of Parkin-associated endothelin receptor-like receptor (Pael-R), a substrate of Parkin, leads to endoplasmic reticulum stress, causing neuronal death. We previously reported that human E3 HRD1 in the endoplasmic reticulum protects against endoplasmic reticulum stress-induced apoptosis. This study shows that HRD1 was expressed in substantia nigra pars compacta (SNC) dopaminergic neurons and interacted with Pael-R through the HRD1 proline-rich region, promoting the ubiquitylation and degradation of Pael-R. Furthermore, the disruption of endogenous HRD1 by small interfering RNA (siRNA) induced Pael-R accumulation and caspase-3 activation. We also found that ATF6 overexpression, which induced HRD1, accelerated and caused Pael-R degradation; the suppression of HRD1 expression by siRNA partially prevents this degradation. These results suggest that in addition to Parkin, HRD1 is also involved in the degradation of Pael-R. 相似文献
993.
Anne E. Powell Chia-Yi Shung Katherine W. Saylor Karin A. Müllendorf Joseph B. Weiss Melissa H. Wong 《Stem cell research》2010,4(1):3-9
Asymmetric stem cell division has emerged as a major regulatory mechanism for physiologic control of stem cell numbers. Reinvigoration of the cancer stem cell theory suggests that tumorigenesis may be regulated by maintaining the balance between asymmetric and symmetric cell division. Therefore, mutations affecting this balance could result in aberrant expansion of stem cells. Although a number of molecules have been implicated in regulation of asymmetric stem cell division, here, we highlight known tumor suppressors with established roles in this process. While a subset of these tumor suppressors were originally defined in developmental contexts, recent investigations reveal they are also lost or mutated in human cancers. Mutations in tumor suppressors involved in asymmetric stem cell division provide mechanisms by which cancer stem cells can hyperproliferate and offer an intriguing new focus for understanding cancer biology. Our discussion of this emerging research area derives insight from a frontier area of basic science and links these discoveries to human tumorigenesis. This highlights an important new focus for understanding the mechanism underlying expansion of cancer stem cells in driving tumorigenesis. 相似文献
994.
Schollenberger L Gronemeyer T Huber CM Lay D Wiese S Meyer HE Warscheid B Saffrich R Peränen J Gorgas K Just WW 《PloS one》2010,5(11):e13886
The current view of peroxisome inheritance provides for the formation of new peroxisomes by both budding from the endoplasmic reticulum and autonomous division. Here we investigate peroxisome-cytoskeleton interactions and show by proteomics, biochemical and immunofluorescence analyses that actin, non-muscle myosin IIA (NMM IIA), RhoA, Rho kinase II (ROCKII) and Rab8 associate with peroxisomes. Our data provide evidence that (i) RhoA in its inactive state, maintained for example by C. botulinum toxin exoenzyme C3, dissociates from peroxisomes enabling microtubule-based peroxisomal movements and (ii) dominant-active RhoA targets to peroxisomes, uncouples the organelles from microtubules and favors Rho kinase recruitment to peroxisomes. We suggest that ROCKII activates NMM IIA mediating local peroxisomal constrictions. Although our understanding of peroxisome-cytoskeleton interactions is still incomplete, a picture is emerging demonstrating alternate RhoA-dependent association of peroxisomes to the microtubular and actin cytoskeleton. Whereas association of peroxisomes to microtubules clearly serves bidirectional, long-range saltatory movements, peroxisome-acto-myosin interactions may support biogenetic functions balancing peroxisome size, shape, number, and clustering. 相似文献
995.
Karin Vitzthum Cristian Scutaru Lindy Musial-Bright David Quarcoo Tobias Welte Michael Spallek Beatrix Groneberg-Kloft 《PloS one》2010,5(6)
Background
Passive exposure to environmental tobacco smoke (ETS) is estimated to exert a major burden of disease. Currently, numerous countries have taken legal actions to protect the population against ETS. Numerous studies have been conducted in this field. Therefore, scientometric methods should be used to analyze the accumulated data since there is no such approach available so far.Methods and Results
A combination of scientometric methods and novel visualizing procedures were used, including density-equalizing mapping and radar charting techniques. 6,580 ETS-related studies published between 1900 and 2008 were identified in the ISI database. Using different scientometric approaches, a continuous increase of both quantitative and qualitative parameters was found. The combination with density-equalizing calculations demonstrated a leading position of the United States (2,959 items published) in terms of quantitative research activities. Charting techniques demonstrated that there are numerous bi- and multilateral networks between different countries and institutions in this field. Again, a leading position of American institutions was found.Conclusions
This is the first comprehensive scientometric analysis of data on global scientific activities in the field of environmental tobacco smoke research. The present findings can be used as a benchmark for funding allocation processes. 相似文献996.
Exosomes communicate protective messages during oxidative stress; possible role of exosomal shuttle RNA 总被引:1,自引:0,他引:1
Background
Exosomes are small extracellular nanovesicles of endocytic origin that mediate different signals between cells, by surface interactions and by shuttling functional RNA from one cell to another. Exosomes are released by many cells including mast cells, dendritic cells, macrophages, epithelial cells and tumour cells. Exosomes differ compared to their donor cells, not only in size, but also in their RNA, protein and lipid composition.Methodology/Principal Findings
In this study, we show that exosomes, released by mouse mast cells exposed to oxidative stress, differ in their mRNA content. Also, we show that these exosomes can influence the response of other cells to oxidative stress by providing recipient cells with a resistance against oxidative stress, observed as an attenuated loss of cell viability. Furthermore, Affymetrix microarray analysis revealed that the exosomal mRNA content not only differs between exosomes and donor cells, but also between exosomes derived from cells grown under different conditions; oxidative stress and normal conditions. Finally, we also show that exposure to UV-light affects the biological functions associated with exosomes released under oxidative stress.Conclusions/Significance
These results argue that the exosomal shuttle of RNA is involved in cell-to-cell communication, by influencing the response of recipient cells to an external stress stimulus. 相似文献997.
998.
Background
Growing evidence indicates that elevated body temperature after stroke is associated with unfavorable outcome. The aim of the current study was to investigate which factors predict temperature elevation within 48 h of stroke onset. Specifically, we hypothesized that temperature elevation would be associated with stroke symptom severity and that hemorrhagic stroke would cause a more pronounced temperature increase compared to ischemic stroke.Methods
The medical records of 400 stroke patients were retrospectively reviewed. Multiple linear regression analysis was used to determine which factors were associated with elevated body temperature.Results
Several factors were significantly associated with peak body temperature (the highest recorded body temperature) within 48 h of stroke onset: stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS) (regression coefficient; (RC) 0.022), female gender (RC 0.157), tympanic/non-rectal temperature reading (RC ?0.265), swallowing difficulties (RC 0.335), intubation (RC 0.470), antipyretic treatment (RC 0.563), and C-reactive protein?>?50 or signs of infection at admission (RC 0.298). Contrary to our expectations, patients with intracerebral hemorrhage did not have higher peak body temperatures than patients with ischemic stroke.Conclusions
In conclusion, temperature elevation within the first 48 h of stroke onset is common, can be partially predicted using information at admission and is strongly associated with stroke severity. The strong association with stroke severity may, at least partly, explain the previously described association between post-stroke temperature elevation and unfavorable outcome.999.
Factors Affecting Women's Autonomous Decision Making In Research Participation Amongst Yoruba Women Of Western Nigeria
下载免费PDF全文
![点击此处可从《Developing world bioethics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Chitu Womehoma Princewill Ayodele S. Jegede Karin Nordström Bolatito Lanre‐Abass Bernice Simone Elger 《Developing world bioethics》2017,17(1):40-49
Research is a global enterprise requiring participation of both genders for generalizable knowledge; advancement of science and evidence based medical treatment. Participation of women in research is necessary to reduce the current bias that most empirical evidence is obtained from studies with men to inform health care and related policy interventions. Various factors are assumed to limit autonomy amongst the Yoruba women of western Nigeria. This paper seeks to explore the experience and understanding of autonomy by the Yoruba women in relation to research participation. Focus is on factors that affect women's autonomous decision making in research participation. An exploratory qualitative approach comprising four focus group discussions, 42 in‐depth interviews and 14 key informant interviews was used. The study permits a significant amount of triangulation, as opinions of husbands and religious leaders are also explored. Interviews and discussions were audiotaped and transcribed verbatim. Content analysis was employed for data analysis. Findings show that concepts of autonomy varied amongst the Yoruba women. Patriarchy, religion and culture are conceived to have negative impact on the autonomy of women in respect to research participation. Among the important findings are: 1) male dominance is strongly emphasized by religious leaders who should teach equality, 2) while men feel that by making decisions for women, they are protecting them, the women on the other hand see this protection as a way of limiting their autonomy. We recommend further studies to develop culturally appropriate and workable recruitment methods to increase women's participation in research. 相似文献
1000.
David Renman Erik Lundberg Ulf Gunnarsson Karin Strigård 《World journal of surgical oncology》2017,15(1):222