全文获取类型
收费全文 | 59484篇 |
免费 | 5698篇 |
国内免费 | 22篇 |
专业分类
65204篇 |
出版年
2023年 | 243篇 |
2022年 | 504篇 |
2021年 | 1005篇 |
2020年 | 632篇 |
2019年 | 807篇 |
2018年 | 992篇 |
2017年 | 864篇 |
2016年 | 1476篇 |
2015年 | 2442篇 |
2014年 | 2705篇 |
2013年 | 3158篇 |
2012年 | 4210篇 |
2011年 | 4073篇 |
2010年 | 2581篇 |
2009年 | 2345篇 |
2008年 | 3383篇 |
2007年 | 3433篇 |
2006年 | 3259篇 |
2005年 | 3092篇 |
2004年 | 3029篇 |
2003年 | 2772篇 |
2002年 | 2704篇 |
2001年 | 872篇 |
2000年 | 713篇 |
1999年 | 815篇 |
1998年 | 854篇 |
1997年 | 589篇 |
1996年 | 513篇 |
1995年 | 470篇 |
1994年 | 498篇 |
1993年 | 494篇 |
1992年 | 623篇 |
1991年 | 499篇 |
1990年 | 486篇 |
1989年 | 490篇 |
1988年 | 440篇 |
1987年 | 408篇 |
1986年 | 403篇 |
1985年 | 377篇 |
1984年 | 434篇 |
1983年 | 398篇 |
1982年 | 419篇 |
1981年 | 382篇 |
1980年 | 395篇 |
1979年 | 310篇 |
1978年 | 299篇 |
1977年 | 263篇 |
1976年 | 257篇 |
1974年 | 233篇 |
1973年 | 208篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
821.
822.
Zhenyu Jia Michael B. Lilly James A. Koziol Xin Chen Xiao-Qin Xia Yipeng Wang Douglas Skarecky Manuel Sutton Anne Sawyers Herbert Ruckle Philip M. Carpenter Jessica Wang-Rodriguez Jun Jiang Mingsen Deng Cong Pan Jian-guo Zhu Christine E. McLaren Michael J. Gurley Chung Lee Michael McClelland Thomas Ahlering Michael W. Kattan Dan Mercola 《PloS one》2014,9(1)
It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies. 相似文献
823.
Esther Nkuipou-Kenfack Flore Duranton Nathalie Gayrard àngel Argilés Ulrika Lundin Klaus M. Weinberger Mohammed Dakna Christian Delles William Mullen Holger Husi Julie Klein Thomas Koeck Petra Zürbig Harald Mischak 《PloS one》2014,9(5)
Chronic kidney disease (CKD) is part of a number of systemic and renal diseases and may reach epidemic proportions over the next decade. Efforts have been made to improve diagnosis and management of CKD. We hypothesised that combining metabolomic and proteomic approaches could generate a more systemic and complete view of the disease mechanisms. To test this approach, we examined samples from a cohort of 49 patients representing different stages of CKD. Urine samples were analysed for proteomic changes using capillary electrophoresis-mass spectrometry and urine and plasma samples for metabolomic changes using different mass spectrometry-based techniques. The training set included 20 CKD patients selected according to their estimated glomerular filtration rate (eGFR) at mild (59.9±16.5 mL/min/1.73 m2; n = 10) or advanced (8.9±4.5 mL/min/1.73 m2; n = 10) CKD and the remaining 29 patients left for the test set. We identified a panel of 76 statistically significant metabolites and peptides that correlated with CKD in the training set. We combined these biomarkers in different classifiers and then performed correlation analyses with eGFR at baseline and follow-up after 2.8±0.8 years in the test set. A solely plasma metabolite biomarker-based classifier significantly correlated with the loss of kidney function in the test set at baseline and follow-up (ρ = −0.8031; p<0.0001 and ρ = −0.6009; p = 0.0019, respectively). Similarly, a urinary metabolite biomarker-based classifier did reveal significant association to kidney function (ρ = −0.6557; p = 0.0001 and ρ = −0.6574; p = 0.0005). A classifier utilising 46 identified urinary peptide biomarkers performed statistically equivalent to the urinary and plasma metabolite classifier (ρ = −0.7752; p<0.0001 and ρ = −0.8400; p<0.0001). The combination of both urinary proteomic and urinary and plasma metabolic biomarkers did not improve the correlation with eGFR. In conclusion, we found excellent association of plasma and urinary metabolites and urinary peptides with kidney function, and disease progression, but no added value in combining the different biomarkers data. 相似文献
824.
Satish K. Madala Ramakrishna Edukulla Mukta Phatak Stephanie Schmidt Cynthia Davidson Thomas H. Acciani Thomas R. Korfhagen Mario Medvedovic Timothy D. LeCras Kimberly Wagner William D. Hardie 《PloS one》2014,9(1)
Pulmonary fibrosis is often triggered by an epithelial injury resulting in the formation of fibrotic lesions in the lung, which progress to impair gas exchange and ultimately cause death. Recent clinical trials using drugs that target either inflammation or a specific molecule have failed, suggesting that multiple pathways and cellular processes need to be attenuated for effective reversal of established and progressive fibrosis. Although activation of MAPK and PI3K pathways have been detected in human fibrotic lung samples, the therapeutic benefits of in vivo modulation of the MAPK and PI3K pathways in combination are unknown. Overexpression of TGFα in the lung epithelium of transgenic mice results in the formation of fibrotic lesions similar to those found in human pulmonary fibrosis, and previous work from our group shows that inhibitors of either the MAPK or PI3K pathway can alter the progression of fibrosis. In this study, we sought to determine whether simultaneous inhibition of the MAPK and PI3K signaling pathways is a more effective therapeutic strategy for established and progressive pulmonary fibrosis. Our results showed that inhibiting both pathways had additive effects compared to inhibiting either pathway alone in reducing fibrotic burden, including reducing lung weight, pleural thickness, and total collagen in the lungs of TGFα mice. This study demonstrates that inhibiting MEK and PI3K in combination abolishes proliferative changes associated with fibrosis and myfibroblast accumulation and thus may serve as a therapeutic option in the treatment of human fibrotic lung disease where these pathways play a role. 相似文献
825.
826.
Cristina L. Vázquez Thomas R. Lerner Bahram Kasmapour Gang Pei Achim Gronow Maria V. Bianco Federico C. Blanco Christopher K. E. Bleck Robert Geffers Fabiana Bigi Wolf‐Rainer Abraham Maximiliano G. Gutierrez 《Cellular microbiology》2014,16(9):1425-1440
Some intracellular bacteria are known to cause long‐term infections that last decades without compromising the viability of the host. Although of critical importance, the adaptations that intracellular bacteria undergo during this long process of residence in a host cell environment remain obscure. Here, we report a novel experimental approach to study the adaptations of mycobacteria imposed by a long‐term intracellular lifestyle. Selected Mycobacterium bovis BCG through continuous culture in macrophages underwent an adaptation process leading to impaired phenolic glycolipids (PGL) synthesis, improved usage of glucose as a carbon source and accumulation of neutral lipids. These changes correlated with increased survival of mycobacteria in macrophages and mice during re‐infection and also with the specific expression of stress‐ and survival‐related genes. Our findings identify bacterial traits implicated in the establishment of long‐term cellular infections and represent a tool for understanding the physiological states and the environment that bacteria face living in fluctuating intracellular environments. 相似文献
827.
828.
Kelly Brooks Max Ranall Loredana Spoerri Alex Stevenson Gency Gunasingh Sandra Pavey Fred Meunier Thomas J. Gonda Brian Gabrielli 《Pigment cell & melanoma research》2014,27(5):813-821
Melanoma cell lines are commonly defective for the G2‐phase cell cycle checkpoint that responds to incomplete catenation of the replicated chromosomes. Here, we demonstrate that melanomas defective for this checkpoint response are less sensitive to genotoxic stress, suggesting that the defective cell lines compensated for the checkpoint loss by increasing their ability to cope with DNA damage. We performed an siRNA kinome screen to identify kinases responsible and identified PI3K pathway components. Checkpoint‐defective cell lines were three‐fold more sensitive to small molecule inhibitors of PI3K. The PI3K inhibitor PF‐05212384 promoted apoptosis in the checkpoint‐defective lines, and the increased sensitivity to PI3K inhibition correlated with increased levels of activated Akt. This work demonstrates that increased PI3K pathway activation is a necessary adaption for the continued viability of melanomas with a defective decatenation checkpoint. 相似文献
829.
Microbial gardening in the ocean's twilight zone: Detritivorous metazoans benefit from fragmenting,rather than ingesting,sinking detritus 下载免费PDF全文
830.
Volatile Compounds of Viola odorata Absolutes: Identification of Odorant Active Markers to Distinguish Plants Originating from France and Egypt 下载免费PDF全文
Laure Saint‐Lary Céline Roy Jean‐Philippe Paris Pascal Tournayre Jean‐Louis Berdagué Olivier P. Thomas Xavier Fernandez 《化学与生物多样性》2014,11(6):843-860
Absolutes isolated from Viola odorata leaves, valuable materials for the flavor and fragrance industry, were studied. Violets are mainly cultivated in France and Egypt and extracted locally. The absolutes of the two origins showed different olfactory profiles both in top and heart notes, as evidenced by sensory analysis. The aims of this study were i) to characterize the volatile compounds, ii) to determine the odorant‐active ones, and iii) to identify some markers of the plant origin. Two complementary analytical methods were used for these purposes, i.e., headspace solid‐phase microextraction (HS‐SPME) using different fiber coatings followed by GC/MS analysis and gas chromatography – olfactometry/mass spectrometry (GC‐O/MS) applied to violet leaf extracts. From a total of 70 identified compounds, 61 have never been reported so far for this species, 17 compounds were characterized by both techniques (with seven among them known from the literature), 23 compounds were solely identified by HS‐SPME GC/MS (among them only two being already mentioned as components of violet absolutes in the literature), and, finally, 30 compounds were only identified by GC‐O/MS. According to the HS‐SPME GC/MS analyses, ethyl hexanoate and (2E,6Z)‐nona‐2,6‐dienol were specific volatile compounds of the sample with French origin, while (E,E)‐hepta‐2,4‐dienal, hexanoic acid, limonene, tridecane, and eugenol were specific of the samples with Egyptian origin. Additional compounds that were not detected by HS‐SPME GC/MS analysis were revealed by GC‐O analyses, some of them being markers of origin. Pent‐1‐en‐3‐ol, 3‐methylbut‐2‐enal, 2‐methoxy‐3‐(1‐methylethyl)pyrazine, 4‐ethylbenzaldehyde, β‐phenethyl formate, and 2‐methoxy‐3‐(2‐methylpropyl)pyrazine revealed to be odorant markers of the French sample, whereas cis‐rose oxide, trans‐rose oxide, and 3,5,5‐trimethylcyclohex‐2‐enone were odorant markers of the Egyptian samples. 相似文献