全文获取类型
收费全文 | 2473篇 |
免费 | 229篇 |
专业分类
2702篇 |
出版年
2023年 | 16篇 |
2022年 | 25篇 |
2021年 | 51篇 |
2020年 | 38篇 |
2019年 | 40篇 |
2018年 | 66篇 |
2017年 | 49篇 |
2016年 | 64篇 |
2015年 | 107篇 |
2014年 | 120篇 |
2013年 | 125篇 |
2012年 | 166篇 |
2011年 | 179篇 |
2010年 | 97篇 |
2009年 | 84篇 |
2008年 | 133篇 |
2007年 | 126篇 |
2006年 | 127篇 |
2005年 | 94篇 |
2004年 | 95篇 |
2003年 | 93篇 |
2002年 | 83篇 |
2001年 | 61篇 |
2000年 | 56篇 |
1999年 | 46篇 |
1998年 | 32篇 |
1997年 | 13篇 |
1996年 | 20篇 |
1995年 | 22篇 |
1994年 | 18篇 |
1993年 | 22篇 |
1992年 | 38篇 |
1991年 | 22篇 |
1990年 | 34篇 |
1989年 | 24篇 |
1988年 | 20篇 |
1987年 | 22篇 |
1986年 | 20篇 |
1985年 | 30篇 |
1984年 | 13篇 |
1982年 | 13篇 |
1980年 | 15篇 |
1979年 | 20篇 |
1978年 | 17篇 |
1977年 | 12篇 |
1975年 | 13篇 |
1974年 | 12篇 |
1972年 | 17篇 |
1971年 | 12篇 |
1970年 | 11篇 |
排序方式: 共有2702条查询结果,搜索用时 15 毫秒
181.
Zoltán Kellermayer Viktória Fisi Martina Mihalj Gergely Berta József Kóbor Péter Balogh 《The journal of histochemistry and cytochemistry》2014,62(6):436-449
The marginal zone (MZ) region of the spleen plays an important role in leukocyte traffic and the removal of blood-borne pathogens by resident macrophages. Macrophage receptor with a collagenous structure (MARCO), expressed by MZ macrophages, recognizes several microbial ligands and is also involved in the retention of MZ B cells. Here, we report that MARCO is also associated with follicular dendritic cells (FDCs) in the spleen. In its FDC-associated form MARCO is arranged in 0.3–0.5-μm diameter granular-fibrillar structures with an appearance similar to the white pulp conduit system formed by fibroblastic reticular cells (FRCs), but with different compartment preference. The follicular display of MARCO resists irradiation and requires the presence of both MZ macrophages and differentiated FDCs. The follicular delivery of MARCO is independent from the shuffling of marginal zone B cells, and it persists after clodronate liposome-mediated depletion of MZ macrophages. Our findings thus indicate that MARCO is distributed to both MZ and follicles within the spleen into conduit-like structures, where FDC-bound MARCO may mediate communication between the stromal microenvironments of MZ and follicles. 相似文献
182.
Olga Nagy Margit Pál Andor Udvardy Christine AM Shirras Imre Boros Alan D Shirras Péter Deák 《Cell division》2012,7(1):1-15
Background
The spindle assembly checkpoint (SAC) inhibits anaphase progression in the presence of insufficient kinetochore-microtubule attachments, but cells can eventually override mitotic arrest by a process known as mitotic slippage or adaptation. This is a problem for cancer chemotherapy using microtubule poisons.Results
Here we describe mitotic slippage in yeast bub2?? mutant cells that are defective in the repression of precocious telophase onset (mitotic exit). Precocious activation of anaphase promoting complex/cyclosome (APC/C)-Cdh1 caused mitotic slippage in the presence of nocodazole, while the SAC was still active. APC/C-Cdh1, but not APC/C-Cdc20, triggered anaphase progression (securin degradation, separase-mediated cohesin cleavage, sister-chromatid separation and chromosome missegregation), in addition to telophase onset (mitotic exit), during mitotic slippage. This demonstrates that an inhibitory system not only of APC/C-Cdc20 but also of APC/C-Cdh1 is critical for accurate chromosome segregation in the presence of insufficient kinetochore-microtubule attachments.Conclusions
The sequential activation of APC/C-Cdc20 to APC/C-Cdh1 during mitosis is central to accurate mitosis. Precocious activation of APC/C-Cdh1 in metaphase (pre-anaphase) causes mitotic slippage in SAC-activated cells. For the prevention of mitotic slippage, concomitant inhibition of APC/C-Cdh1 may be effective for tumor therapy with mitotic spindle poisons in humans. 相似文献183.
Martina Ferraguti Sergio Magallanes Jéssica Jiménez-Peñuela Josué Martínez-de la Puente Luz Garcia-Longoria Jordi Figuerola Jaime Muriel Tamer Albayrak Staffan Bensch Camille Bonneaud Rohan H. Clarke Gábor Á. Czirják Dimitar Dimitrov Kathya Espinoza John G. Ewen Farah Ishtiaq Wendy Flores-Saavedra László Zsolt Garamszegi Olof Hellgren Dita Horakova Kathryn P. Huyvaert Henrik Jensen Asta Križanauskienė Marcos R. Lima Charlene Lujan-Vega Eyðfinn Magnussen Lynn B. Martin Kevin D. Matson Anders Pape Møller Pavel Munclinger Vaidas Palinauskas Péter L. Pap Javier Pérez-Tris Swen C. Renner Robert Ricklefs Sergio Scebba Ravinder N. M. Sehgal Manuel Soler Eszter Szöllősi Gediminas Valkiūnas Helena Westerdahl Pavel Zehtindjiev Alfonso Marzal 《Global Ecology and Biogeography》2023,32(5):809-823
Aim
The increasing spread of vector-borne diseases has resulted in severe health concerns for humans, domestic animals and wildlife, with changes in land use and the introduction of invasive species being among the main possible causes for this increase. We explored several ecological drivers potentially affecting the local prevalence and richness of avian malaria parasite lineages in native and introduced house sparrows (Passer domesticus) populations.Location
Global.Time period
2002–2019.Major taxa studied
Avian Plasmodium parasites in house sparrows.Methods
We analysed data from 2,220 samples from 69 localities across all continents, except Antarctica. The influence of environment (urbanization index and human density), geography (altitude, latitude, hemisphere) and time (bird breeding season and years since introduction) were analysed using generalized additive mixed models (GAMMs) and random forests.Results
Overall, 670 sparrows (30.2%) were infected with 22 Plasmodium lineages. In native populations, parasite prevalence was positively related to urbanization index, with the highest prevalence values in areas with intermediate urbanization levels. Likewise, in introduced populations, prevalence was positively associated with urbanization index; however, higher infection occurred in areas with either extreme high or low levels of urbanization. In introduced populations, the number of parasite lineages increased with altitude and with the years elapsed since the establishment of sparrows in a new locality. Here, after a decline in the number of parasite lineages in the first 30 years, an increase from 40 years onwards was detected.Main conclusions
Urbanization was related to parasite prevalence in both native and introduced bird populations. In invaded areas, altitude and time since bird introduction were related to the number of Plasmodium lineages found to be infecting sparrows. 相似文献184.
185.
Miklós Z Ivanics T Roemen TH van der Vusse GJ Dézsi L Szekeres M Kemecsei P Tóth A Kollai M Ligeti L 《Molecular and cellular biochemistry》2003,250(1-2):115-124
The main aim of this study was to assess the kinetics of intracellular free calcium (Ca2+
i) handling by isolated rat hearts rendered ischemic for 30 min followed by 30 min of reperfusion analyzing the upstroke and downslope of the Ca2+
i transient. Changes in mechanical performance and degradation of membrane phospholipids – estimated by tissue arachidonic acid content – were correlated with Ca2+
i levels of the heart. The fluorescence ratio technique was applied to estimate Ca2+
i. The disappearance of mechanical activity of the heart preceded that of the Ca2+
i transient in the first 2 min of ischemia. The slope of upstroke of the Ca2+
i transient, reflecting Ca2+ release, decreased by 60%, while the duration of the downslope of the transient, reflecting Ca2+ sequestration, expressed a significant prolongation (105 ± 17 vs. 149 ± 39 msec) during the first 3 min of ischemia. At about 20 min of ischemia end-diastolic pressure expressed a 3.5-fold increase (contracture) when the fluorescence ratio showed a 2-fold elevation. Reperfusion was accompanied with a further precipitous increase in end-diastolic pressure, while resting Ca2+
i remained at end-ischemic levels. Increases in the arachidonic acid (AA) content of the ischemic and postischemic hearts were proportional to Ca2+
i levels. In summary, the present findings indicate that both calcium release and removal are hampered during the early phase of ischemia. Moreover, a critical level of Ca2+
i and a critical duration of ischemia may exist to provoke contracture of the heart. Upon reperfusion the hearts show membrane phospholipid degradation and signs of stunning exemplified by elevated AA levels, partial recovery of Ca2+
i handling and sustained depression of mechanical performance. 相似文献
186.
Saskia Lüde Michael T?r?k Sandy Dieterle René J?ggi Karin Berger Büter Stephan Kr?henbühl 《Phytomedicine》2008,15(1-2):120-131
Kava extracts are used widely for different purposes and were thought to be safe. Recently, several cases of hepatotoxicity have been published. To explore possible mechanisms of kava hepatotoxicity, we prepared and analyzed three different kava extracts (a methanolic and an acetonic root and a methanolic leaf extract), and investigated their toxicity on HepG2 cells and isolated rat liver mitochondria. All three extracts showed cytotoxicity starting at a concentration of 50 microg/ml (lactate dehydrogenase leakage) or 1 microg/ml (MTT test). The mitochondrial membrane potential was decreased (root extracts starting at 50 microg/ml) and the respiratory chain inhibited and uncoupled (root extracts) or only uncoupled (leaf extract) at 150 microg/ml, and mitochondrial beta-oxidation was inhibited by all extracts starting at 100 microg/ml. The ratio oxidized to reduced glutathione was increased in HepG2 cells, whereas the cellular ATP content was maintained. Induction of apoptosis was demonstrated by all extracts at a concentration of 150 microg/ml. These results indicate that the kava extracts are toxic to mitochondria, leading to inhibition of the respiratory chain, increased ROS production, a decrease in the mitochondrial membrane potential and eventually to apoptosis of exposed cells. In predisposed patients, mitochondrial toxicity of kava extract may explain hepatic adverse reactions of this drug. 相似文献
187.
M Bálint I Wolf A Tarcsafalvi J Gergely F A Sréter 《Archives of biochemistry and biophysics》1978,190(2):793-799
The two essential thiol groups of myosin, SH-1 and SH-2, have been localized in an ~ 20K segment of the heavy chain by analysis of the distribution of radioactivity after tryptic digestion of tryptic heavy meromyosin (HMM) or papain-HMM subfragment-1, both labeled at SH-1 and SH-2 with [14C]iodoacetamide and [14C]N-ethyl maleimide, respectively. The results are discussed in the framework of earlier work (Bálint, M., Sréter, F. A., Wolf, I., Nagy, B., and Gergely, J. (1975) J. Biol. Chem. 250, 6168–6177) on the tryptic fragmentation of myosin heavy chain and in the light of more recent work on the location of a fragment that reacts with a photoaffinity analog of ATP (Szilágyi, L., Bálint, M., Sréter, F. A., and Gergely, J. (1978) Fed. Proc. 37, 1695) and of suggestions concerning the binding of ATP in the region containing the SH-1 and SH-2 (Elzinga, M., and Collins, J. H. (1977) Proc. Nat. Acad. Sci. USA74, 4281–4284). 相似文献
188.
E. Hampton Sessions Michael Smolinski Bo Wang Bozena Frackowiak Sarwat Chowdhury Yan Yin Yen Ting Chen Claudia Ruiz Li Lin Jennifer Pocas Thomas Schröter Michael D. Cameron Philip LoGrasso Yangbo Feng Thomas D. Bannister 《Bioorganic & medicinal chemistry letters》2010,20(6):1939-1943
Rho Kinase (ROCK) is a serine/threonine kinase whose inhibition could prove beneficial in numerous therapeutic areas. We have developed a promising class of ATP-competitive inhibitors based upon a benzimidazole scaffold, which show excellent potency toward ROCK (IC50 <10 nM). This report details the optimization of selectivity for ROCK over other related kinases such as Protein kinase A (PKA). 相似文献
189.
Effect of cross-reinnervation on physiological parameters and on properties of myosin and sarcoplasmic reticulum of fast and slow muscles of the rabbit 总被引:3,自引:0,他引:3 下载免费PDF全文
Cross-reinnvervation of fast (extensor digitorum longus) and slow (soleus) twitch muscles of the rabbit showed essentially complete fast to slow and slow to fast conversion, respectively, 11-12 mo after surgery with respect to a number of physiological parameters including intrinsic shortening, velocity, and isometric twitch time to peak. There was pronounced bu incomplete biochemical conversion as judged by Ca2+ uptake by sarcoplasmic reticulum, myosin ATPase, alkali lability, and light chain complement. The question of trophic substances of neural origin is discussed in light of the fact that chronic stimulation for 15 wk of a fast muscle produces complete biochemical and physiological conversion to the slow type. 相似文献
190.
Spectral and kinetic characteristics of fluorescence from isolated reaction centers of photosynthetic purple bacteria Rhodobacter sphaeroides and Rhodobacter capsulatus were measured at room temperature under rectangular shape of excitation at 810 nm. The kinetics of fluorescence at 915 nm reflected redox changes due to light and dark reactions in the donor and acceptor quinone complex of the reaction center as identified by absorption changes at 865 nm (bacteriochlorophyll dimer) and 450 nm (quinones) measured simultaneously with the fluorescence. Based on redox titration and gradual bleaching of the dimer, the yield of fluorescence from reaction centers could be separated into a time-dependent (originating from the dimer) and a constant part (coming from contaminating pigment (detached bacteriochlorin)). The origin was also confirmed by the corresponding excitation spectra of the 915 nm fluorescence. The ratio of yields of constant fluorescence over variable fluorescence was much smaller in Rhodobacter sphaeroides (0.15±0.1) than in Rhodobacter capsulatus (1.2±0.3). It was shown that the changes in fluorescence yield reflected the disappearance of the dimer and the quenching by the oxidized primary quinone. The redox changes of the secondary quinone did not have any influence on the yield but excess quinone in the solution quenched the (constant part of) fluorescence. The relative yields of fluorescence in different redox states of the reaction center were tabulated. The fluorescence of the dimer can be used as an effective tool in studies of redox reactions in reaction centers, an alternative to the measurements of absorption kinetics.Abbreviations Bchl
bacteriochlorophyll
- Bpheo
bacteriopheophytin
- D
electron donor to P+
- P
bacteriochlorophyll dimer
- Q
quinone acceptor
- QA
primary quinone acceptor
- QB
secondary quinone acceptor
- RC
reaction center protein
- UQ6
ubiquinone-30 相似文献