全文获取类型
收费全文 | 8709篇 |
免费 | 680篇 |
专业分类
9389篇 |
出版年
2023年 | 89篇 |
2022年 | 128篇 |
2021年 | 253篇 |
2020年 | 135篇 |
2019年 | 179篇 |
2018年 | 215篇 |
2017年 | 199篇 |
2016年 | 305篇 |
2015年 | 471篇 |
2014年 | 518篇 |
2013年 | 662篇 |
2012年 | 742篇 |
2011年 | 691篇 |
2010年 | 408篇 |
2009年 | 441篇 |
2008年 | 526篇 |
2007年 | 448篇 |
2006年 | 424篇 |
2005年 | 409篇 |
2004年 | 374篇 |
2003年 | 330篇 |
2002年 | 317篇 |
2001年 | 102篇 |
2000年 | 67篇 |
1999年 | 85篇 |
1998年 | 94篇 |
1997年 | 80篇 |
1996年 | 63篇 |
1995年 | 50篇 |
1994年 | 46篇 |
1993年 | 49篇 |
1992年 | 36篇 |
1991年 | 28篇 |
1990年 | 29篇 |
1989年 | 27篇 |
1988年 | 22篇 |
1987年 | 29篇 |
1986年 | 13篇 |
1985年 | 28篇 |
1984年 | 31篇 |
1983年 | 24篇 |
1982年 | 24篇 |
1981年 | 22篇 |
1980年 | 14篇 |
1978年 | 15篇 |
1977年 | 23篇 |
1975年 | 11篇 |
1974年 | 17篇 |
1973年 | 12篇 |
1972年 | 11篇 |
排序方式: 共有9389条查询结果,搜索用时 10 毫秒
991.
Juan Manuel Mancilla-Leytón Jesús Cambrollé ángel Martín Vicente 《Plant Ecology》2012,213(9):1503-1510
Seed predation has traditionally been considered as simply a progressive loss of seeds. However, partial consumption of tree seeds may actually assist regeneration. We quantified partial consumption of acorns by the common rabbit (Oryctolagus cuniculus) in a cork oak forest in southwest Spain (Do?ana Natural Park). To examine the effects of partial consumption on germination and seedling emergence, we simulated two different levels of acorn predation (30 and 50?% cotyledon loss, representing light and heavy partial consumption, respectively). One-third of the sampled acorns presented evidence of consumption but most of the damage caused by partial consumption did not affect the acorn embryo (damage was mainly to non-vital parts of the propagule). Partial consumption caused more rapid germination and emergence than that was observed in intact acorns, but germination and emergence rate was unaffected. Heavy consumption of the acorn caused differences in root and shoot biomass as a consequence of cotyledon loss. In this greenhouse study, partial consumption was non-lethal to the acorns, and cotyledon biomass loss did not decrease the probability of successful establishment. Partially consumed seeds can therefore contribute significantly to the natural regeneration of Quercus coccifera, although it would be beneficial to conduct long-term studies focusing on seed traits and animal behaviour under field conditions. 相似文献
992.
Fortuny G López-Cano M Susín A Herrera B 《Computer methods in biomechanics and biomedical engineering》2012,15(2):195-201
We are interested in studying the genesis of a very common pathology: the human inguinal hernia. How the human inguinal hernia appears is not definitively clear, but it is accepted that it is caused by a combination of mechanical and biochemical alterations, and that muscular simulation plays an important role in this. This study proposes a model to explain how some physical parameters affect the ability to simulate the region dynamically and how these parameters are involved in generating inguinal hernias. We are particularly interested in understanding the mechanical alterations in the inguinal region because little is known about them or how they behave dynamically. Our model corroborates the most important theories regarding the generation of inguinal hernias and is an initial approach to numerically evaluating this affection. 相似文献
993.
994.
de Gonzalo-Calvo D de Luxán-Delgado B Rodríguez-González S García-Macia M Suárez FM Solano JJ Rodríguez-Colunga MJ Coto-Montes A 《Cytokine》2012,58(2):193-198
In the present investigation we have analyzed the association between functional dependence and inflammatory biomarkers using the Barthel Index (BI) and the Katz Index (KI). This analysis may contribute to translational medicine by incorporating the clinical and laboratory data to better understand the relationship between chronic inflammation and functional dependence in the elderly population. The ultimate goal of this study was to identify possible useful biomarkers of functional dependence in the elderly. Participants in this study consisted of 120 older subjects (90 women and 30 men; range 68-105 years) who were selected from the Santa Teresa nursing home (Oviedo, Spain). We studied functional status using the following tools to diagnose the functional dependence by clinicians: BI and KI for activities of daily living. We analyzed morbidity, sociodemographic characteristics and a panel of inflammatory and inflammatory-related markers. In linear regression models adjusted by age, sex, anti-inflammatory drug use and morbid conditions high levels of interleukin 6 (IL-6) and soluble TNF receptor-I (sTNF-RI) were associated with functional dependence as measured using BI and KI. Elevated levels of red blood cell distribution width (RDW) were also associated with functional dependence measured using the KI after adjusting for the same potential confounders. The current results suggest that high IL-6, sTNF-RI and RDW levels are associated with the functional dependence in the elderly population. The results are consistent with the presumed underlying biological mechanism, in which the up-regulation of inflammatory mediators is associated with functional dependence in elderly subjects. 相似文献
995.
The molecular graphics program Sculptor and the command-line suite Situs are software packages for the integration of biophysical data across spatial resolution scales. Herein, we provide an overview of recently developed tools relevant to cryo-electron tomography (cryo-ET), with an emphasis on functionality supported by Situs 2.7.1 and Sculptor 2.1.1. We describe a work flow for automatically segmenting filaments in cryo-ET maps including denoising, local normalization, feature detection, and tracing. Tomograms of cellular actin networks exhibit both cross-linked and bundled filament densities. Such filamentous regions in cryo-ET data sets can then be segmented using a stochastic template-based search, VolTrac. The approach combines a genetic algorithm and a bidirectional expansion with a tabu search strategy to localize and characterize filamentous regions. The automated filament segmentation by VolTrac compares well to a manual one performed by expert users, and it allows an efficient and reproducible analysis of large data sets. The software is free, open source, and can be used on Linux, Macintosh or Windows computers. 相似文献
996.
Eduardo Díaz-Rubio Auxiliadora Gómez-Espa?a Bartomeu Massutí Javier Sastre Margarita Reboredo José Luis Manzano Fernando Rivera MaJosé Safont Clara Montagut Encarnación González Manuel Benavides Eugenio Marcuello Andrés Cervantes Purificación Martínez de Prado Carlos Fernández-Martos Antonio Arrivi Inmaculada Bando Enrique Aranda Spanish Cooperative Group for the Treatment of Digestive Tumors 《PloS one》2012,7(10)
Background
In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates.Methodology/Principal Findings
KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p = 0.0038; HR: 1.40; 95% CI:1.12–1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p = 0.0002; HR: 1.55; 95% CI: 1.23–1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p = 0.0054; OR: 1.77; 95% CI: 1.18–2.64).Conclusions/Significance
This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses. 相似文献997.
J Zhuo EH Tan B Yan L Tochhawng M Jayapal S Koh HK Tay SK Maciver SC Hooi M Salto-Tellez AP Kumar YC Goh YC Lim CT Yap 《PloS one》2012,7(8):e43594
Gelsolin is a cytoskeletal protein which participates in actin filament dynamics and promotes cell motility and plasticity. Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apoptotic and pro-migratory functions and is critical for invasion of some types of tumor cells. We found that gelsolin was highly expressed at tumor borders infiltrating into adjacent liver tissues, as examined by immunohistochemistry. Although gelsolin contributes to lamellipodia formation in migrating cells, the mechanisms by which it induces tumor invasion are unclear. Gelsolin's influence on the invasive activity of colorectal cancer cells was investigated using overexpression and small interfering RNA knockdown. We show that gelsolin is required for invasion of colorectal cancer cells through matrigel. Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrix-degrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion. The enhanced invasiveness of gelsolin-overexpressing cells was attenuated by treatment with function-blocking antibodies to either uPA or its receptor uPAR, indicating that uPA/uPAR activity is crucial for gelsolin-dependent invasion. In summary, our data reveals novel functions of gelsolin in colorectal tumor cell invasion through its modulation of the uPA/uPAR cascade, with potentially important roles in colorectal tumor dissemination to metastatic sites. 相似文献
998.
M González-González L Muñoz-Bellvis C Mackintosh C Fontanillo ML Gutiérrez MM Abad O Bengoechea C Teodosio E Fonseca M Fuentes J De Las Rivas A Orfao J María Sayagués 《PloS one》2012,7(8):e42683
Background
Most sporadic colorectal cancer (sCRC) deaths are caused by metastatic dissemination of the primary tumor. New advances in genetic profiling of sCRC suggest that the primary tumor may contain a cell population with metastatic potential. Here we compare the cytogenetic profile of primary tumors from liver metastatic versus non-metastatic sCRC.Methodology/Principal Findings
We prospectively analyzed the frequency of numerical/structural abnormalities of chromosomes 1, 7, 8, 13, 14, 17, 18, 20, and 22 by iFISH in 58 sCRC patients: thirty-one non-metastatic (54%) vs. 27 metastatic (46%) disease. From a total of 18 probes, significant differences emerged only for the 17p11.2 and 22q11.2 chromosomal regions. Patients with liver metastatic sCRC showed an increased frequency of del(17p11.2) (10% vs. 67%;p<.001) and del(22q11.2) (0% vs. 22%;p = .02) versusnon-metastatic cases. Multivariate analysis of prognostic factors for overall survival (OS) showed that the only clinical and cytogenetic parameters that had an independent adverse impact on patient outcome were the presence of del(17p) with a 17p11.2 breakpoint and del(22q11.2). Based on these two cytogenetic variables, patients were classified into three groups: low- (no adverse features), intermediate- (one adverse feature) and high-risk (two adverse features)- with significantly different OS rates at 5-years (p<.001): 92%, 53% and 0%, respectively.Conclusions/Significance
Our results unravel the potential implication of del(17p11.2) in sCRC patients with liver metastasis as this cytogenetic alteration appears to be intrinsically related to an increased metastatic potential and a poor outcome, providing additional prognostic information to that associated with other cytogenetic alterations such as del(22q11.2). Additional prospective studies in larger series of patients would be required to confirm the clinical utility of the new prognostic markers identified. 相似文献999.
This study evaluated the effects of bone marrow-derived mesenchymal stem cells (BMSCs) or their conditioned medium (CM) on the repair and prevention of Acute Kidney Injury (AKI) induced by gentamicin (G). Animals received daily injections of G up to 20 days. On the 10(th) day, injections of BMSCs, CM, CM+trypsin, CM+RNase or exosome-like microvesicles extracted from the CM were administered. In the prevention groups, the animals received the BMSCs 24 h before or on the 5(th) day of G treatment. Creatinine (Cr), urea (U), FENa and cytokines were quantified. The kidneys were evaluated using hematoxylin/eosin staining and immunohystochemistry. The levels of Cr, U and FENa increased during all the periods of G treatment. The BMSC transplantation, its CM or exosome injections inhibited the increase in Cr, U, FENa, necrosis, apoptosis and also increased cell proliferation. The pro-inflammatory cytokines decreased while the anti-inflammatory cytokines increased compared to G. When the CM or its exosomes were incubated with RNase (but not trypsin), these effects were blunted. The Y chromosome was not observed in the 24-h prevention group, but it persisted in the kidney for all of the periods analyzed, suggesting that the injury is necessary for the docking and maintenance of BMSCs in the kidney. In conclusion, the BMSCs and CM minimized the G-induced renal damage through paracrine effects, most likely through the RNA carried by the exosome-like microvesicles. The use of the CM from BMSCs can be a potential therapeutic tool for this type of nephrotoxicity, allowing for the avoidance of cell transplantations. 相似文献
1000.