全文获取类型
收费全文 | 12252篇 |
免费 | 1071篇 |
国内免费 | 800篇 |
出版年
2024年 | 13篇 |
2023年 | 300篇 |
2022年 | 338篇 |
2021年 | 405篇 |
2020年 | 457篇 |
2019年 | 567篇 |
2018年 | 547篇 |
2017年 | 458篇 |
2016年 | 445篇 |
2015年 | 466篇 |
2014年 | 703篇 |
2013年 | 1079篇 |
2012年 | 539篇 |
2011年 | 640篇 |
2010年 | 545篇 |
2009年 | 603篇 |
2008年 | 610篇 |
2007年 | 689篇 |
2006年 | 628篇 |
2005年 | 624篇 |
2004年 | 478篇 |
2003年 | 361篇 |
2002年 | 376篇 |
2001年 | 248篇 |
2000年 | 208篇 |
1999年 | 208篇 |
1998年 | 182篇 |
1997年 | 180篇 |
1996年 | 108篇 |
1995年 | 135篇 |
1994年 | 138篇 |
1993年 | 101篇 |
1992年 | 88篇 |
1991年 | 71篇 |
1990年 | 72篇 |
1989年 | 50篇 |
1988年 | 39篇 |
1987年 | 40篇 |
1986年 | 25篇 |
1985年 | 55篇 |
1984年 | 70篇 |
1983年 | 35篇 |
1982年 | 51篇 |
1981年 | 45篇 |
1980年 | 28篇 |
1979年 | 25篇 |
1978年 | 16篇 |
1977年 | 7篇 |
1976年 | 7篇 |
1973年 | 6篇 |
排序方式: 共有10000条查询结果,搜索用时 46 毫秒
31.
Harish Kumar Jayant B. Udgaonkar 《Protein science : a publication of the Protein Society》2021,30(4):785
Amyloid fibrillar aggregates isolated from the brains of patients with neurodegenerative diseases invariably have post‐translational modifications (PTMs). The roles that PTMs play in modulating the structures and polymorphism of amyloid aggregates, and hence their ability to catalyze the conversion of monomeric protein to their fibrillar structure is, however, poorly understood. This is particularly true in the case of tau aggregates, where specific folds of fibrillar tau have been implicated in specific tauopathies. Several PTMs, including acetylation at Lys 280, increase aggregation of tau in the brain, and increase neurodegeneration. In this study, tau‐K18 K280Q, in which the Lys 280 → Gln mutation is used to mimic acetylation at Lys 280, is shown, using HX‐MS measurements, to form fibrils with a structural core that is longer than that of tau‐K18 fibrils. Measurements of critical concentrations show that the binding affinity of monomeric tau‐K18 for its fibrillar counterpart is only marginally more than that of monomeric tau‐K18 K280Q for its fibrillar counterpart. Quantitative analysis of the kinetics of seeded aggregation, using a simple Michaelis–Menten‐like model, in which the monomer first binds and then undergoes conformational conversion to β‐strand, shows that the fibrils of tau‐K18 K280Q convert monomeric protein more slowly than do fibrils of tau‐K18. In contrast, monomeric tau‐K18 K280Q is converted faster to fibrils than is monomeric tau‐K18. Thus, the effect of Lys 280 acetylation on tau aggregate propagation in brain cells is expected to depend on the amount of acetylated tau present, and on whether the propagating seed is acetylated at Lys 280 or not. 相似文献
32.
Y. Saijo S. Takeda A. Scherer T. Kobayashi Y. Mada H. Taniguchi M. Yao S. Wakatsuki 《Protein science : a publication of the Protein Society》1997,6(4):916-918
Troponin is a ternary protein complex consisting of subunits TnC. TnI, and TnT, and plays a key role in calcium regulation of the skeletal and cardiac muscle contraction. In the present study, a partial complex (CI47) was prepared from Escherichia coli-expressed rabbit skeletal muscle TnC and fragment 1-47 of TnI, which is obtained by chemical cleavage of an E. coli-expressed mutant of rabbit skeletal muscle TnI. Within the ternary troponin complex, CI47 is thought to form a core that is resistant to proteolytic digestion, and the interaction within CI47 likely maintains the integrity of the troponin complex. Complex CI47 was crystallized in the presence of sodium citrate. The addition of trehalose improved the diffraction pattern of the crystals substantially. The crystal lattice belongs to the space group P3(1)(2)21, with unit cell dimensions a = b = 48.2 A, c = 162 A. The asymmetric unit presumably contains one CI47 complex. Soaking with p-chloromercuribenzenesulfonate (PCMBS) resulted in loss of isomorphism, but enhanced the quality of the crystals. The crystals diffracted up to 2.3 A resolution, with completeness of 91% and R(merge) = 6.4%. The crystals of PCMBS-derivative should be suitable for X-ray studies using the multiple-wavelength anomalous diffraction technique. This is the first step for elucidating the structure of the full troponin complex. 相似文献
33.
34.
Jarle Tryti Nordeide 《Journal of fish biology》2020,96(2):288-296
This paper highlights possible effects of physical and chemical mechanisms of formalin fixation and preservation on biological tissue and reviews the consequent potential inaccuracies on estimates of body mass of small fishes fixed and preserved in formalin. Twenty-six papers including 65 independent experiments with 35 species which examine effects of formalin on body mass estimates on small fishes are included. The effect of the formalin on the specimens depends on the salinity of the water used to dilute the commercial formalin (usually 1:9 formalin: water) before being used to fixate and preserve fish. Mean wet body mass of the specimens from the studies using seawater or fresh water diluted formalin deceases by 13% and increases by 7%, respectively, from before to after being immersed in formalin. The same trend is found with condition factor in the few papers that report this parameter. Body length decreases on average by c. 2% in fixated and preserved fish regardless of whether the formalin is diluted in seawater or fresh water. 相似文献
35.
36.
Wei Liu Yaoting Sun Weigang Ge Fangfei Zhang Lin Gan Yi Zhu Tiannan Guo Kexin Liu 《Molecular & cellular proteomics : MCP》2022,21(2):100187
Drug resistance is a critical obstacle to effective treatment in patients with chronic myeloid leukemia. To understand the underlying resistance mechanisms in response to imatinib mesylate (IMA) and adriamycin (ADR), the parental K562 cells were treated with low doses of IMA or ADR for 2 months to generate derivative cells with mild, intermediate, and severe resistance to the drugs as defined by their increasing resistance index. PulseDIA-based (DIA [data-independent acquisition]) quantitative proteomics was then employed to reveal the proteome changes in these resistant cells. In total, 7082 proteins from 98,232 peptides were identified and quantified from the dataset using four DIA software tools including OpenSWATH, Spectronaut, DIA-NN, and EncyclopeDIA. Sirtuin signaling pathway was found to be significantly enriched in both ADR-resistant and IMA-resistant K562 cells. In particular, isocitrate dehydrogenase (NADP(+)) 2 was identified as a potential drug target correlated with the drug resistance phenotype, and its inhibition by the antagonist AGI-6780 reversed the acquired resistance in K562 cells to either ADR or IMA. Together, our study has implicated isocitrate dehydrogenase (NADP(+)) 2 as a potential target that can be therapeutically leveraged to alleviate the drug resistance in K562 cells when treated with IMA and ADR. 相似文献
37.
38.
Scaling of metabolic rate with body mass and temperature in teleost fish 总被引:27,自引:0,他引:27
39.
T. R. Shankar Raman 《Journal of biosciences》1997,22(2):203-218
Chital or axis deer (Axis axis) form fluid groups that change in size temporally and in relation to habitat. Predictions of hypotheses relating animal density,
rainfall, habitat structure, and breeding seasonality, to changes in chital group size were assessed simultaneously using
multiple regression models of monthly data collected over a 2 yr period in Guindy National Park, in southern India. Over 2,700
detections of chital groups were made during four seasons in three habitats (forest, scrubland and grassland). In scrubland
and grassland, chital group size was positively related to animal density, which increased with rainfall. This suggests that
in these habitats, chital density increases in relation to food availability, and group sizes increase due to higher encounter
rate and fusion of groups. The density of chital in forest was inversely related to rainfall, but positively to the number
of fruiting tree species and availability of fallen litter, their forage in this habitat. There was little change in mean
group size in the forest, although chital density more than doubled during the dry season and summer. Dispersion of food items
or the closed nature of the forest may preclude formation of larger groups. At low densities, group sizes in all three habitats
were similar. Group sizes increased with chital density in scrubland and grassland, but more rapidly in the latter—leading
to a positive relationship between openness and mean group size at higher densities. It is not clear, however, that this relationship
is solely because of the influence of habitat structure. The rutting index (monthly percentage of adult males in hard antler)
was positively related to mean group size in forest and scrubland, probably reflecting the increase in group size due to solitary
males joining with females during the rut. The fission-fusion system of group formation in chital is thus interactively influenced
by several factors. Aspects that need further study, such as interannual variability, are highlighted. 相似文献
40.
Lalita K. Shekhawat 《Preparative biochemistry & biotechnology》2013,43(6):623-638
AbstractLiquid chromatography is considered to be the bottleneck for purification of therapeutic proteins. Development and optimization of chromatography process is a cumbersome activity due to the increasing complexities in the types and content of impurities present in the high product titer cell culture harvest obtained from the upstream processing. Further, regulatory expectations are continuously rising with the recent initiatives of quality by design and process analytical technology expecting the manufacturer to have a deeper understanding of the process and the product. Mechanistic modeling is one approach to gain this deeper understanding of a process step. It involves modeling of the underlying physicochemical processes. A well calibrated model with acceptable predictability can be very effective in both process optimization and process characterization activities. In this paper we provide an overview of mechanistic modeling of liquid chromatography. We discuss the various components that such a model entails and also presents the status quo of this area. 相似文献