全文获取类型
收费全文 | 4155篇 |
免费 | 362篇 |
国内免费 | 3篇 |
学科分类
生物科学 | 4520篇 |
出版年
2024年 | 2篇 |
2023年 | 17篇 |
2022年 | 38篇 |
2021年 | 58篇 |
2020年 | 37篇 |
2019年 | 46篇 |
2018年 | 63篇 |
2017年 | 54篇 |
2016年 | 103篇 |
2015年 | 195篇 |
2014年 | 212篇 |
2013年 | 250篇 |
2012年 | 344篇 |
2011年 | 330篇 |
2010年 | 205篇 |
2009年 | 187篇 |
2008年 | 237篇 |
2007年 | 288篇 |
2006年 | 304篇 |
2005年 | 280篇 |
2004年 | 239篇 |
2003年 | 241篇 |
2002年 | 215篇 |
2001年 | 43篇 |
2000年 | 41篇 |
1999年 | 50篇 |
1998年 | 77篇 |
1997年 | 44篇 |
1996年 | 34篇 |
1995年 | 39篇 |
1994年 | 28篇 |
1993年 | 29篇 |
1992年 | 29篇 |
1991年 | 21篇 |
1990年 | 21篇 |
1989年 | 12篇 |
1988年 | 11篇 |
1987年 | 14篇 |
1986年 | 11篇 |
1985年 | 10篇 |
1984年 | 11篇 |
1983年 | 10篇 |
1982年 | 12篇 |
1981年 | 8篇 |
1979年 | 8篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1967年 | 2篇 |
1966年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有4520条查询结果,搜索用时 15 毫秒
101.
Ekkehard Schütz Christin Wehrhahn Marius Wanjek Ralf Bortfeld Wilhelm E. Wemheuer Julia Beck Bertram Brenig 《PloS one》2016,11(4)
BackgroundWith the availability of massive SNP data for several economically important cattle breeds, haplotype tests have been performed to identify unknown recessive disorders. A number of so-called lethal haplotypes, have been uncovered in Holstein Friesian cattle and, for at least seven of these, the causative mutations have been identified in candidate genes. However, several lethal haplotypes still remain elusive. Here we report the molecular genetic causes of lethal haplotype 5 (HH5) and cholesterol deficiency (CDH). A targeted enrichment for the known genomic regions, followed by massive parallel sequencing was used to interrogate for causative mutations in a case/control approach.MethodsTargeted enrichment for the known genomic regions, followed by massive parallel sequencing was used in a case/control approach. PCRs for the causing mutations were developed and compared to routine imputing in 2,100 (HH5) and 3,100 (CDH) cattle.ResultsHH5 is caused by a deletion of 138kbp, spanning position 93,233kb to 93,371kb on chromosome 9 (BTA9), harboring only dimethyl-adenosine transferase 1 (TFB1M). The deletion breakpoints are flanked by bovine long interspersed nuclear elements Bov-B (upstream) and L1ME3 (downstream), suggesting a homologous recombination/deletion event. TFB1M di-methylates adenine residues in the hairpin loop at the 3’-end of mitochondrial 12S rRNA, being essential for synthesis and function of the small ribosomal subunit of mitochondria. Homozygous TFB1M-/- mice reportedly exhibit embryonal lethality with developmental defects. A 2.8% allelic frequency was determined for the German HF population. CDH results from a 1.3kbp insertion of an endogenous retrovirus (ERV2-1-LTR_BT) into exon 5 of the APOB gene at BTA11:77,959kb. The insertion is flanked by 6bp target site duplications as described for insertions mediated by retroviral integrases. A premature stop codon in the open reading frame of APOB is generated, resulting in a truncation of the protein to a length of only <140 amino acids. Such early truncations have been shown to cause an inability of chylomicron excretion from intestinal cells, resulting in malabsorption of cholesterol. The allelic frequency of this mutation in the German HF population was 6.7%, which is substantially higher than reported so far. Compared to PCR assays inferring the genetic variants directly, the routine imputing used so far showed a diagnostic sensitivity of as low as 91% (HH5) and 88% (CDH), with a high specificity for both (≥99.7%).ConclusionWith the availability of direct genetic tests it will now be possible to more effectively reduce the carrier frequency and ultimately eliminate the disorders from the HF populations. Beside this, the fact that repetitive genomic elements (RE) are involved in both diseases, underline the evolutionary importance of RE, which can be detrimental as here, but also advantageous over generations. 相似文献
102.
Johnsen Bjarne Kaschubowski Klaus Eric Nader Sorush Schneider Enja Nicola Jan-Andrei Fliegert Ralf Wolf Insa M. A. Guse Andreas H. Nikolaev Viacheslav O. Koch-Nolte Friedrich Haag Friedrich 《Purinergic signalling》2019,15(2):155-166
Purinergic Signalling - ATP and its metabolites are important extracellular signal transmitters acting on purinergic P2 and P1 receptors. Most cells can actively secrete ATP in response to a... 相似文献
103.
Chandrasekaran Uma Burkhoff Daniel Ishikawa Kiyotake Swain Lija Sunagawa Kenji Mller Jacob Santos-Gallego Carlos Annamalai Shiva Udelson James Westenfeld Ralf Kapur Navin Qiao Xiaoying Wiora Julian Schfer Andreas Bernhardt Alexander Kochar Ajar Kloner Robert Faraz Haroon 《BMC cardiovascular disorders》2019,19(2):1-17
104.
105.
Ralf Müller-Rath Stefan Andereya Sascha Gravius Dieter Christian Wirtz Rudolf Marx Torsten Mumme 《Biomedizinische Technik》2007,52(6):391-397
Cemented femoral stems have shown decreased longevity compared to cementless implants in hip revision arthroplasty. The aim of this study was to evaluate the effect of an amphiphilic bonder on bone cement stability in a biomechanical femur expulsion test. A simplified hip simulator test setup with idealised femur stem specimens was carried out. The stems were implanted into bovine femurs (group 1: no bonder, n=10; group 2: bonder including glutaraldehyde, n=10; group 3: bonder without glutaraldehyde, n=10). A dynamic loading (maximum load: 800 N; minimum load: 100 N; frequency: 3 Hz; 105 cycles) was performed. Subsequently, the stem specimens were expulsed axially out of their implant beds and maximum load at failure was recorded. The static controls showed a mean maximum load to failure of 4123 N in group 1, 8357.5 N in group 2 and 5830.8 N in group 3. After dynamic loading, the specimens of group 2 reached the highest load to failure (8191.5 N), followed by group 3 (5649.5 N) and group 1 (3462 N), respectively. In group 2, we observed nine periprosthetic fractures at a load of 8400 N without signs of interface loosening. Application of an amphiphilic bonder led to a significant improvement of bonding stability, especially when glutaraldehyde was added to the bonder. This technique might offer an increased longevity of cemented femur revision stems in total hip replacement. 相似文献
106.
107.
The misfolding and fibril formation of alpha-synuclein plays an important role in neurodegenerative diseases such as Parkinson disease. Here we used electron paramagnetic resonance spectroscopy, together with site-directed spin labeling, to investigate the structural features of alpha-synuclein fibrils. We generated fibrils from a total of 83 different spin-labeled derivatives and observed single-line, exchange-narrowed EPR spectra for the majority of all sites located within the core region of alpha-synuclein fibrils. Such exchange narrowing requires the orbital overlap between multiple spin labels in close contact. The core region of alpha-synuclein fibrils must therefore be arranged in a parallel, in-register structure wherein same residues from different molecules are stacked on top of each other. This parallel, in-register core region extends from residue 36 to residue 98 and is tightly packed. Only a few sites within the core region, such as residues 62-67 located at the beginning of the NAC region, as well as the N- and C-terminal regions outside the core region, are significantly less ordered. Together with the accessibility measurements that suggest the location of potential beta-sheet regions within the fibril, the data provide significant structural constraints for generating three-dimensional models. Furthermore, the data support the emerging view that parallel, in-register structure is a common feature shared by a number of naturally occurring amyloid fibrils. 相似文献
108.
109.
110.
Dityatev A Brückner G Dityateva G Grosche J Kleene R Schachner M 《Developmental neurobiology》2007,67(5):570-588
Extracellular matrix molecules--including chondroitin sulfate proteoglycans, hyaluronan, and tenascin-R--are enriched in perineuronal nets (PNs) associated with subsets of neurons in the brain and spinal cord. In the present study, we show that similar cell type-dependent extracellular matrix aggregates are formed in dissociated cell cultures prepared from early postnatal mouse hippocampus. Starting from the 5th day in culture, accumulations of lattice-like extracellular structures labeled with Wisteria floribunda agglutinin were detected at the cell surface of parvalbumin-expressing interneurons, which developed after 2-3 weeks into conspicuous PNs localized around synaptic contacts at somata and proximal dendrites, as well as around axon initial segments. Physiological recording and intracellular labeling of PN-expressing neurons revealed that these are large fast-spiking interneurons with morphological characteristics of basket cells. To study mechanisms of activity-dependent formation of PNs, we performed pharmacological analysis and found that blockade of action potentials, transmitter release, Ca2+ permeable AMPA subtype of glutamate receptors or L-type Ca2+ voltage-gated channels strongly decreased the extracellular accumulation of PN components in cultured neurons. Thus, we suggest that Ca2+ influx via AMPA receptors and L-type channels is necessary for activity-dependent formation of PNs. To study functions of chondroitin sulfate-rich PNs, we treated cultures with chondroitinase ABC that resulted in a prominent reduction of several major PN components. Removal of PNs did not affect the number and distribution of perisomatic GABAergic contacts but increased the excitability of interneurons in cultures, implicating the extracellular matrix of PNs in regulation of interneuronal activity. 相似文献