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Miriam Andrés Mónica Bravo Maria Antonia Buil Marta Calbet Jordi Castro Teresa Domènech Peter Eichhorn Manel Ferrer Elena Gómez Martin D. Lehner Imma Moreno Richard S. Roberts Sara Sevilla 《Bioorganic & medicinal chemistry letters》2013,23(11):3349-3353
High throughput screening identified the pyrazole-4-acetic acid substructure as CRTh2 receptor antagonists. Optimisation of the compounds uncovered a tight SAR but also identified some low nanomolar inhibitors. 相似文献
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Anabel Fernndez‐Iglesias Martí Ortega‐Ribera Sergi Guix‐Muntet Jordi Gracia‐Sancho 《Journal of cellular and molecular medicine》2019,23(2):877-886
Liver cells isolated from pre‐clinical models are essential tools for studying liver (patho)physiology, and also for screening new therapeutic options. We aimed at developing a new antibody‐free isolation method able to obtain the four main hepatic cell types (hepatocytes, liver sinusoidal endothelial cells [LSEC], hepatic macrophages [HMΦ] and hepatic stellate cells [HSC]) from a single rat liver. Control and cirrhotic (CCl4 and TAA) rat livers (n = 6) were perfused, digested with collagenase and mechanically disaggregated obtaining a multicellular suspension. Hepatocytes were purified by low revolution centrifugations while non‐parenchymal cells were subjected to differential centrifugation. Two different fractions were obtained: HSC and mixed LSEC + HMΦ. Further LSEC and HMΦ enrichment was achieved by selective adherence time to collagen‐coated substrates. Isolated cells showed high viability (80%‐95%) and purity (>95%) and were characterized as functional: hepatocytes synthetized albumin and urea, LSEC maintained endocytic capacity and in vivo fenestrae distribution, HMΦ increased expression of inflammatory markers in response to LPS and HSC were activated upon in vitro culture. The 4 in 1 protocol allows the simultaneous isolation of highly pure and functional hepatic cell sub‐populations from control or cirrhotic single livers without antibody selection. 相似文献
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The interaction of phenethyl alcohol with model membranes and its effect on translocation of the chemically prepared mitochondrial precursor protein apocytochrome c across a lipid bilayer was studied. Phenethyl alcohol efficiently penetrates into monolayers and causes acyl chain disordering judged from deuterium nuclear magnetic resonance measurements with specific acyl chain-deuterated phospholipids. Translocation of apocytochrome c across a phospholipid bilayer was stimulated on addition of phenethyl alcohol indicating that the efficiency of translocation of this precursor protein is enhanced due to a disorder of the acyl chain region of the bilayer. 相似文献
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Habitat patchiness and plant species richness 总被引:2,自引:0,他引:2
The pattern of woody species richness decline with a decrease in woody vegetation cover was studied within a tallgrass prairie. The decline in species richness is highly non-linear, with a well-defined threshold below which species richness collapses. This relationship can be understood after considering information on how landscape structure changes with woody vegetation cover, and how species richness is related to landscape structure. 相似文献
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Longitudinal Evaluation of the Structure of Replicating and Circulating Hepatitis C Virus Quasispecies in Nonprogressive Chronic Hepatitis C Patients 下载免费PDF全文
Beatriz Cabot María Martell Juan I. Esteban Maria Piron Teresa Otero Rafael Esteban Jaime Guardia Jordi Gmez 《Journal of virology》2001,75(24):12005-12013
In previous cross-sectional studies, we demonstrated that, in most patients with chronic hepatitis C, the composition and complexity of the circulating hepatitis C virus (HCV) population do not coincide with those of the virus replicating in the liver. In the subgroup of patients with similar complexities in both compartments, the ratio of quasispecies complexity in the liver to that in serum (liver/serum complexity ratio) of paired samples correlated with disease stage. In the present study we investigated the dynamic behavior of viral population parameters in consecutive paired liver and serum samples, obtained 3 to 6 years apart, from four chronic hepatitis C patients with persistently normal transaminases and stable liver histology. We sequenced 359 clones of a genomic fragment encompassing the E2(p7)-NS2 junction, in two consecutive liver-serum sample pairs from the four patients and in four intermediate serum samples from one of the patients. The results show that the liver/serum complexity ratio is not stable but rather fluctuates widely over time. Hence, the liver/serum complexity ratio does not identify a particular group of patients but a particular state of the infecting quasispecies. Phylogenetic analysis and signature mutation patterns showed that virtually all circulating sequences originated from sequences present in the liver specimens. The overall behavior of the circulating viral quasispecies appears to originate from changes in the relative replication kinetics of the large mutant spectrum present in the infected liver. 相似文献
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The distribution of different macroinvertebrate groups inhabiting the littoral zone of 82 mountain lakes in the Pyrenees was
investigated in relation to the altitudinal environmental gradient. For each lake, altitude, longitude and latitude, together
with 28 environmental variables, relating to chemical and physical characteristics and to lake general productivity, were
considered. Using Principal Component Analysis (PCA) we showed that the altitudinal environmental gradient (i.e. altitude
and altitude-related variables) represented the largest gradient of environmental variability. We found that incidence was
related to altitude in about 50% of macroinvertebrate groups, most relationships being inverse, and also that the number of
macroinvertebrate groups found per lake was better described by a second-order polynomial function than by simple linear regression.
However, this relationship was linear for a subset of high-altitude lakes above 2,500 m a.s.l., suggesting an ecological threshold
around this altitude. Redundancy Analyses (RDAs) showed the importance of environmental factors varying with altitude for
the distribution of macroinvertebrate groups. Organic matter, salmonid presence, fine substrate dominance, macrophyte coverage,
temperature and altitude by itself were, in this order, the most relevant factors. Partial RDAs showed that different combinations
of these variables contributed to the explanation of the distribution of each group. However, the variable that uniquely explained
most variability differed from group to group. We conclude that the altitudinal gradient is a multi-faceted ecological factor,
which impinges on each group by means of some specific environmental variable(s) that are particularly relevant for the life
history of that group. 相似文献
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Body growth and life history in wild mountain gorillas (Gorilla beringei beringei) from Volcanoes National Park,Rwanda 下载免费PDF全文