全文获取类型
收费全文 | 4363篇 |
免费 | 320篇 |
国内免费 | 1篇 |
专业分类
4684篇 |
出版年
2023年 | 18篇 |
2022年 | 39篇 |
2021年 | 106篇 |
2020年 | 63篇 |
2019年 | 81篇 |
2018年 | 107篇 |
2017年 | 90篇 |
2016年 | 145篇 |
2015年 | 194篇 |
2014年 | 225篇 |
2013年 | 260篇 |
2012年 | 403篇 |
2011年 | 354篇 |
2010年 | 234篇 |
2009年 | 176篇 |
2008年 | 259篇 |
2007年 | 276篇 |
2006年 | 269篇 |
2005年 | 198篇 |
2004年 | 225篇 |
2003年 | 208篇 |
2002年 | 191篇 |
2001年 | 33篇 |
2000年 | 33篇 |
1999年 | 47篇 |
1998年 | 54篇 |
1997年 | 45篇 |
1996年 | 29篇 |
1995年 | 42篇 |
1994年 | 25篇 |
1993年 | 17篇 |
1992年 | 23篇 |
1991年 | 24篇 |
1990年 | 32篇 |
1989年 | 14篇 |
1988年 | 16篇 |
1987年 | 12篇 |
1986年 | 10篇 |
1985年 | 10篇 |
1984年 | 11篇 |
1983年 | 13篇 |
1982年 | 5篇 |
1981年 | 13篇 |
1980年 | 8篇 |
1979年 | 7篇 |
1978年 | 6篇 |
1977年 | 9篇 |
1975年 | 12篇 |
1973年 | 5篇 |
1972年 | 2篇 |
排序方式: 共有4684条查询结果,搜索用时 15 毫秒
151.
Identification of a nucleo-cytoplasmic ionic pathway by osmotic shock in isolated mouse liver nuclei
Summary The observation that the nuclear envelope outer mem brane contains ion channels raises the question of whether these conductances
communicate between the cytosol and the nuclear envelope cisternae or between the cytosol and the cytoplasm. Failure to detect
large, nonselective holes using the patch-clamp technique has led to the speculation that ion channels and nuclear pores are
in fact the same.
In this paper we present evidence that the ionic channel, recorded in isolated liver nuclei with the patch-clamp configura
tion of “nucleus-attached,” spans the double membrane of the envelope, providing a direct contact between nucleoplasm and
cytoplasm. 相似文献
152.
Vito Michele Garrisi Antonio Tufaro Paolo Trerotoli Italia Bongarzone Michele Quaranta Vincenzo Ventrella Stefania Tommasi Gianluigi Giannelli Angelo Paradiso 《PloS one》2012,7(11)
Epidemiological studies suggest a possible association between BMI, diagnosis and clinical-pathological breast cancer characteristics but biological bases for this relationship still remain to be ascertained. Several biological mechanisms play a role in the genesis and progression of breast cancer. This study aimed to investigate relationships between BMI and breast cancer diagnosis/progression in a Southern Italian population and to try to interpret results according to the serum proteomic profile of healthy and breast cancer patients.BMI, presence or absence of breast cancer and its clinical-pathological characteristics were analyzed in a series of 300 breast cancer women and compared with those of 300 healthy women prospectively. To investigate whether obesity is associated with alterations in serum protein profile, SELDI-ToF approach was applied.Alcohol consumption (22.7% vs 11.3%; p<0.001) and postmenopausal status (65.7% vs 52%; p<0.001) but not BMI resulted significantly different in patients vs controls. Conversely, BMI was significantly associated with a larger-tumour size (BMI> = 30 respect to normal weight: OR = 2.49, 95% CI 1.25–4.99, p = 0.0098) and a higher probability of having positive axillary lymph node (OR = 3.67, CI 95% 2.16–6.23, p<0.0001). Multivariate analysis confirmed the association of breast cancer diagnosis with alcohol consumption (OR = 2.28;CI 1.36–3.83; p<0.0018). Serum protein profile revealed the presence of significant (p-value <0,01) differentially expressed peaks m/z 6934, m/z 5066 in high BMI breast cancer patients vs healthy subjects and m/z 6934, m/z 3346 in high vs low BMI breast cancer patients.The analysis of pathological features of cancer indicates that normal weight women have a significantly higher probability of having a smaller breast cancer at time of diagnosis and negative axillary lymph nodes while increased BMI is associated with an altered protein profile in breast cancer patients. Further studies to identify specific proteins found in the serum and their role in breast cancerogenesis and progression are in progress. 相似文献
153.
Thomas Nittoli Marcus P. Kelly Frank Delfino John Rudge Arthur Kunz Thomas Markotan Jan Spink Zhaoyuan Chen Jing Shan Elizabeth Navarro Michele Tait Kathleen Provoncha Jason Giurleo Feng Zhao Xiaobo Jiang Donna Hylton Sosina Makonnen Carlos Hickey Nicholas Papadopoulos 《Bioorganic & medicinal chemistry》2018,26(9):2271-2279
Natural products have been used for many medicinal purposes for centuries. Antibody drug conjugates (ADCs) have utilized this rich source of small molecule therapeutics to produce several clinically useful treatments. ADCs based on the natural product maytansine have been successful clinically. The authors further the utility of the anti-cancer natural product maytansine by developing efficacious payloads and linker-payloads for conjugating to antibodies. The success of our approach was realized in the EGFRvIII targeting ADC EGFRvIII-16. The ADC was able to regress tumors in 2 tumor models (U251/EGFRvIII and MMT/EGFRvIII). When compared to a positive control ADC, the efficacy observed was similar or improved while the isotype control ADCs had no effect. 相似文献
154.
155.
FOXM1 Transcription Factor: A New Component of Chronic Myeloid Leukemia Stem Cell Proliferation Advantage 下载免费PDF全文
Manuela Mancini Fausto Castagnetti Simona Soverini Elisa Leo Caterina De Benedittis Gabriele Gugliotta Gianantonio Rosti Luana Bavaro Sara De Santis Cecilia Monaldi Margherita Martelli Maria Alessandra Santucci Michele Cavo Giovanni Martinelli 《Journal of cellular biochemistry》2017,118(11):3968-3975
156.
Maciej A. Zwieniecki Matthew V. Thompson N. Michele Holbrook 《Journal of Plant Growth Regulation》2003,21(4):315-323
The water uptake region in roots is several hundred times longer than the root diameter. The distributed nature of the uptake zone requires that the hydraulic design of roots be understood by analogy to flow through a porous pipe. Here we present results of an analytical and experimental investigation that allowed an in-depth analysis of root hydraulic properties. Measurements on nodal maize roots confirm the nonlinear distribution of water uptake predicted by the porous pipe model. The major design parameter governing the distribution of water uptake along a porous pipe is the ratio between its axial and radial hydraulic resistance. However, total flow is proportional to the pipe's overall resistance. These results suggest the existence of a tradeoff between the effective utilization of root length and the total capacity for water uptake. 相似文献
157.
Late cytoplasmic maturation of the small ribosomal subunit requires RIO proteins in Saccharomyces cerevisiae 下载免费PDF全文
Vanrobays E Gelugne JP Gleizes PE Caizergues-Ferrer M 《Molecular and cellular biology》2003,23(6):2083-2095
Numerous nonribosomal trans-acting factors involved in pre-rRNA processing have been characterized, but few of them are specifically required for the last cytoplasmic steps of 18S rRNA maturation. We have recently demonstrated that Rrp10p/Rio1p is such a factor. By BLAST analysis, we identified the product of a previously uncharacterized essential gene, YNL207W/RIO2, called Rio2p, that shares 43% sequence similarity with Rrp10p/Rio1p. Rio2p homologues were identified throughout the Archaea and metazoan species. We show that Rio2p is a cytoplasmic-nuclear protein and that its depletion blocks 18S rRNA production, leading to 20S pre-rRNA accumulation. In situ hybridization reveals that in Rio2p-depleted cells, 20S pre-rRNA localizes in the cytoplasm, demonstrating that its accumulation is not due to an export defect. We also show that both Rio1p and Rio2p accumulate in the nucleus of crm1-1 cells at the nonpermissive temperature. Nuclear as well as cytoplasmic Rio2p and Rio1p cosediment with pre-40S particles. These results strongly suggest that Rio2p and Rrp10p/Rio1p are shuttling proteins which associate with pre-40S particles in the nucleus and they are not necessary for export of the pre-40S complexes but are absolutely required for the cytoplasmic maturation of 20S pre-rRNA at site D, leading to mature 40S ribosomal subunits. 相似文献
158.
Weston WM Freeman AB Haberecht C Hackmiller RC Ma L Nugent P Warr E Pisano MM Greene RM 《Life sciences》2002,71(16):1849-1862
159.
160.
Lannie Ligthart Jouke-Jan Hottenga Cathryn M. Lewis Anne E. Farmer Ian W. Craig Gerome Breen Gonneke Willemsen Jacqueline M. Vink Christel M. Middeldorp Enda M. Byrne Andrew C. Heath Pamela A. F. Madden Michele L. Pergadia Grant W. Montgomery Nicholas G. Martin Brenda W. J. H. Penninx Peter McGuffin Dorret I. Boomsma Dale R. Nyholt 《Human genetics》2014,133(2):173-186
Migraine and major depressive disorder (MDD) are comorbid, moderately heritable and to some extent influenced by the same genes. In a previous paper, we suggested the possibility of causality (one trait causing the other) underlying this comorbidity. We present a new application of polygenic (genetic risk) score analysis to investigate the mechanisms underlying the genetic overlap of migraine and MDD. Genetic risk scores were constructed based on data from two discovery samples in which genome-wide association analyses (GWA) were performed for migraine and MDD, respectively. The Australian Twin Migraine GWA study (N = 6,350) included 2,825 migraine cases and 3,525 controls, 805 of whom met the diagnostic criteria for MDD. The RADIANT GWA study (N = 3,230) included 1,636 MDD cases and 1,594 controls. Genetic risk scores for migraine and for MDD were used to predict pure and comorbid forms of migraine and MDD in an independent Dutch target sample (NTR–NESDA, N = 2,966), which included 1,476 MDD cases and 1,058 migraine cases (723 of these individuals had both disorders concurrently). The observed patterns of prediction suggest that the ‘pure’ forms of migraine and MDD are genetically distinct disorders. The subgroup of individuals with comorbid MDD and migraine were genetically most similar to MDD patients. These results indicate that in at least a subset of migraine patients with MDD, migraine may be a symptom or consequence of MDD. 相似文献