全文获取类型
收费全文 | 1265篇 |
免费 | 66篇 |
国内免费 | 5篇 |
专业分类
1336篇 |
出版年
2024年 | 4篇 |
2023年 | 16篇 |
2022年 | 32篇 |
2021年 | 63篇 |
2020年 | 34篇 |
2019年 | 36篇 |
2018年 | 43篇 |
2017年 | 29篇 |
2016年 | 54篇 |
2015年 | 59篇 |
2014年 | 80篇 |
2013年 | 110篇 |
2012年 | 106篇 |
2011年 | 110篇 |
2010年 | 56篇 |
2009年 | 46篇 |
2008年 | 64篇 |
2007年 | 54篇 |
2006年 | 46篇 |
2005年 | 48篇 |
2004年 | 38篇 |
2003年 | 38篇 |
2002年 | 25篇 |
2001年 | 14篇 |
2000年 | 13篇 |
1999年 | 14篇 |
1998年 | 8篇 |
1997年 | 11篇 |
1996年 | 7篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1981年 | 5篇 |
1980年 | 6篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1974年 | 4篇 |
1973年 | 2篇 |
1971年 | 4篇 |
1969年 | 2篇 |
1967年 | 2篇 |
1966年 | 2篇 |
1964年 | 2篇 |
排序方式: 共有1336条查询结果,搜索用时 0 毫秒
11.
Parikh HH Balasubramanian V Chu WL Morris ME Ramanathan M 《Journal of biomolecular screening》1999,4(6):315-318
Because of the need for resource-sparing assays of the solubility of new drug candidates, we sought to develop and validate a rapid method for determining the solubility of nonvolatile pharmaceutical solids in water. Vapor-phase osmometry was used to determine the concentration of drugs in saturated solutions prepared by a rapid ultrasound-mediated dissolution protocol. The osmolality of saturated solutions as measured by the vapor-phase osmometer is an excellent predictor of the solubility of pharmaceutical solids in water. Each osmolality measurement requires less than 10 μl of saturated solution and takes less than 2 min to complete. For small-molecule drugs with solubilities greater than 10 g/kg, osmometry may prove to be a rapid and accurate method for determining the water solubilities of drugs. 相似文献
12.
Munoz Frances M. Patel Priya A. Gao Xinghua Mei Yixiao Xia Jingsheng Gilels Sofia Hu Huijuan 《Purinergic signalling》2020,16(1):97-107
Purinergic Signalling - Astrocytes mediate a remarkable variety of cellular functions, including gliotransmitter release. Under pathological conditions, high concentrations of the purinergic... 相似文献
13.
14.
Arunagiri Kuha Deva Magendhra Rao Vittal Rangan Arvinden Deepa Ramasamy Krishna Patel Balaiah Meenakumari Priya Ramanathan Shirley Sundersingh Velusami Sridevi Thangarajan Rajkumar Zdenko Herceg Harsha Gowda Samson Mani 《Journal of cellular and molecular medicine》2021,25(8):3912-3921
Breast cancer is a major cause of cancer-related death in women worldwide. Non-coding RNAs are a potential resource to be used as an early diagnostic biomarker for breast cancer. Circular RNAs are a recently identified group of non-coding RNA with a significant role in disease development with potential utility in diagnosis/prognosis in cancer. In this study, we identified 26 differentially expressed circular RNAs associated with early-stage breast cancer. RNA sequencing and two circRNA detection tools (find_circ and DCC) were used to understand the circRNA expression signature in breast cancer. We identified hsa_circ_0006743 (circJMJD1C) and hsa_circ_0002496 (circAPPBP1) to be significantly up-regulated in early-stage breast cancer tissues. Co-expression analysis identified four pairs of circRNA-miRNA (hsa_circ_0023990 : hsa-miR-548b-3p, hsa_circ_0016601 : hsa_miR-1246, hsa_circ_0001946 : hsa-miR-1299 and hsa_circ_0000117:hsa-miR-502-5p) having potential interaction. The miRNA target prediction and network analysis revealed mRNA possibly regulated by circRNAs. We have thus identified circRNAs of diagnostic implications in breast cancer and also observed circRNA-miRNA interaction which could be involved in breast cancer development. 相似文献
15.
Priya Gogoi Saedeh Sepehri Yi Zhou Michael A. Gorin Carmela Paolillo Ettore Capoluongo Kyle Gleason Austin Payne Brian Boniface Massimo Cristofanilli Todd M. Morgan Paolo Fortina Kenneth J. Pienta Kalyan Handique Yixin Wang 《PloS one》2016,11(1)
Current analysis of circulating tumor cells (CTCs) is hindered by sub-optimal sensitivity and specificity of devices or assays as well as lack of capability of characterization of CTCs with clinical biomarkers. Here, we validate a novel technology to enrich and characterize CTCs from blood samples of patients with metastatic breast, prostate and colorectal cancers using a microfluidic chip which is processed by using an automated staining and scanning system from sample preparation to image processing. The Celsee system allowed for the detection of CTCs with apparent high sensitivity and specificity (94% sensitivity and 100% specificity). Moreover, the system facilitated rapid capture of CTCs from blood samples and also allowed for downstream characterization of the captured cells by immunohistochemistry, DNA and mRNA fluorescence in-situ hybridization (FISH). In a subset of patients with prostate cancer we compared the technology with a FDA-approved CTC device, CellSearch and found a higher degree of sensitivity with the Celsee instrument. In conclusion, the integrated Celsee system represents a promising CTC technology for enumeration and molecular characterization. 相似文献
16.
Semantic integration to identify overlapping functional modules in protein interaction networks 总被引:4,自引:0,他引:4
Background
The systematic analysis of protein-protein interactions can enable a better understanding of cellular organization, processes and functions. Functional modules can be identified from the protein interaction networks derived from experimental data sets. However, these analyses are challenging because of the presence of unreliable interactions and the complex connectivity of the network. The integration of protein-protein interactions with the data from other sources can be leveraged for improving the effectiveness of functional module detection algorithms. 相似文献17.
18.
Sai Priya Anand Shilei Ding William D. Tolbert Jrmie Prvost Jonathan Richard Hwi Min Gil Gabrielle Gendron-Lepage Wing-Fai Cheung Haifeng Wang Rebecca Pastora Hirak Saxena Warren Wakarchuk Halima Medjahed Bruce D. Wines Mark Hogarth George M. Shaw Malcom A. Martin Dennis R. Burton Lars Hangartner David T. Evans Marzena Pazgier Doug Cossar Michael D. McLean Andrs Finzi 《Journal of virology》2021,95(18)
19.
Arjun H. Ananth Natarajan Manikandan Ravi Kumar Rajan Ramakrishnan Elancheran Kunasekaran Lakshmithendral Muthiah Ramanathan Atanu Bhattacharjee Senthamaraikannan Kabilan 《化学与生物多样性》2020,17(2)
Breast Cancer (BCa) is the most often diagnosed cancer among women who were in the late 1940’s. Breast cancer growth is largely dependent on the expression of estrogen and progesterone receptor. Breast cancer cells may have one, both, or none of these receptors. The treatment for breast cancer may involve surgery, hormonal therapy (Tamoxifen, an aromatase inhibitor, etc.) and oral chemotherapeutic drugs. The molecular docking technique reported the findings on the potential binding modes of the 2‐(2‐bromo‐3‐nitrophenyl)‐5‐phenyl‐1,3,4‐oxadiazole derivatives with the estrogen receptor (PDB ID: 3ERT). The 1,3,4‐oxadiazole derivatives 4a – 4j have been synthesized and described by spectroscopic method. 2‐(2‐Bromo‐6‐nitrophenyl)‐5‐(4‐bromophenyl)‐1,3,4‐oxadiazole ( 4c ) was reconfirmed by single‐crystal XRD. All the compounds have been tested in combination with generic Imatinib pharmaceutical drug against breast cancer cell lines isolated from Caucasian woman MCF‐7, MDA‐MB‐453 and MCF‐10A non‐cancer cell lines. The compounds with the methoxy (in 4c ) and methyl (in 4j ) substitution were shown to have significant cytotoxicity, with 4c showing dose‐dependent activation and decreased cell viability. The mechanism of action was reported by induced apoptosis and tested by a DNA enzyme inhibitor experiment (ELISA) for Methyl Transferase. Molecular dynamics simulations were made for hit molecule 4c to study the stability and interaction of the protein?ligand complex. The toxicity properties of ADME were calculated for all the compounds. All these results provide essential information for further clinical trials. 相似文献
20.
Connecting the geographical occurrence of a species with underlying environmental variables is fundamental for many analyses of life history evolution and for modeling species distributions for both basic and practical ends. However, raw distributional information comes principally in two forms: points of occurrence (specific geographical coordinates where a species has been observed), and expert-prepared range maps. Each form has potential short-comings: range maps tend to overestimate the true occurrence of a species, whereas occurrence points (because of their frequent non-random spatial distribution) tend to underestimate it. Whereas previous comparisons of the two forms have focused on how they may differ when estimating species richness, less attention has been paid to the extent to which the two forms actually differ in their representation of a species’ environmental associations. We assess such differences using the globally distributed avian order Galliformes (294 species). For each species we overlaid range maps obtained from IUCN and point-of-occurrence data obtained from GBIF on global maps of four climate variables and elevation. Over all species, the median difference in distribution centroids was 234 km, and median values of all five environmental variables were highly correlated, although there were a few species outliers for each variable. We also acquired species’ elevational distribution mid-points (mid-point between minimum and maximum elevational extent) from the literature; median elevations from point occurrences and ranges were consistently lower (median −420 m) than mid-points. We concluded that in most cases occurrence points were likely to produce better estimates of underlying environmental variables than range maps, although differences were often slight. We also concluded that elevational range mid-points were biased high, and that elevation distributions based on either points or range maps provided better estimates. 相似文献