全文获取类型
收费全文 | 3061篇 |
免费 | 295篇 |
出版年
2021年 | 34篇 |
2020年 | 13篇 |
2019年 | 26篇 |
2018年 | 35篇 |
2017年 | 29篇 |
2016年 | 53篇 |
2015年 | 90篇 |
2014年 | 140篇 |
2013年 | 169篇 |
2012年 | 206篇 |
2011年 | 197篇 |
2010年 | 129篇 |
2009年 | 123篇 |
2008年 | 161篇 |
2007年 | 170篇 |
2006年 | 182篇 |
2005年 | 176篇 |
2004年 | 167篇 |
2003年 | 143篇 |
2002年 | 166篇 |
2001年 | 35篇 |
2000年 | 36篇 |
1999年 | 57篇 |
1998年 | 57篇 |
1997年 | 48篇 |
1996年 | 44篇 |
1995年 | 43篇 |
1994年 | 33篇 |
1993年 | 37篇 |
1992年 | 47篇 |
1991年 | 41篇 |
1990年 | 40篇 |
1989年 | 32篇 |
1988年 | 37篇 |
1987年 | 17篇 |
1986年 | 16篇 |
1985年 | 30篇 |
1984年 | 33篇 |
1983年 | 21篇 |
1982年 | 33篇 |
1981年 | 26篇 |
1980年 | 24篇 |
1979年 | 16篇 |
1978年 | 17篇 |
1977年 | 16篇 |
1976年 | 11篇 |
1975年 | 9篇 |
1974年 | 10篇 |
1973年 | 12篇 |
1972年 | 10篇 |
排序方式: 共有3356条查询结果,搜索用时 15 毫秒
31.
Gerard A. Kennedy Grahame J. Coleman Stuart M. Armstrong 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1990,166(5):607-618
Summary The effects of restricted feeding schedules on the circadian rhythms of wheel-running of Dasyurus viverrinus were examined under a light/dark cycle and in constant darkness (experiment 1) and in constant light (experiment 2). The results of the 2 experiments showed that: (1) in contrast to the light/dark cycle, restricted feeding is only a weak zeitgeber for the wheel-running activity rhythms of D. viverrinus; (2) restricted feeding elicits meal anticipatory activity in D. viverrinus comparable to that elicited by restricted feeding in the rat; (3) transient cycles of the anticipatory activity free-run with a period different to that of the main component of activity for several cycles after the termination of restricted feeding; and (4) activity suggestive of beating between 2 oscillators occurs during restricted feeding and after the termination of restricted feeding. Taken together the latter 3 observations suggest that the activity rhythms of D. viverrinus are controlled by at least 2 separate circadian oscillators. 相似文献
32.
Danny Burg Dmitri V Filippov Ralph Hermanns Gijs A van der Marel Jacques H van Boom Gerard J Mulder 《Bioorganic & medicinal chemistry》2002,10(1):195-205
Elevated levels of glutathione-S-transferase (GST) isoenzymes are found in many tumor cells and are thought to play a role in the onset of multidrug resistance (MDR). To evaluate the contribution of GST to this process, inhibitors are needed. Glutathione (GSH) conjugates, although good GST inhibitors, cannot be used in vivo, because they are eliminated rapidly. In this paper, we describe the synthesis of a series of novel peptidomimetic glutathione analogues that are stabilized against peptidase mediated breakdown. The peptide bonds in GSH were replaced by isosteres, such as the 'reduced' amide (which was prepared using a novel method), N-methylamide, urethane, and methylene linkages. The in vitro evaluation of the compounds focuses on GST inhibition and stability towards gamma-glutamyl-transpeptidase (gammaGT), the main enzyme involved in GSH breakdown. The compounds were conjugated to the model electrophile ethacrynic acid (EA) to resemble GS-EA, an efficient GST inhibitor. All novel GSH-analogues were shown to inhibit rat liver cytosolic GSTs. Furthermore, peptidomimetic changes of the gamma-glutamyl-cysteine amide bond greatly improved stability towards gammaGT. These compounds may therefore be useful in the design of novel in vivo applicable GST inhibitors. 相似文献
33.
E. R. Jasper Wubs Wim H. van der Putten Simon R. Mortimer Gerard W. Korthals Henk Duyts Roel Wagenaar T. Martijn Bezemer 《Ecology letters》2019,22(7):1145-1151
Recent demonstrations of the role of plant–soil biota interactions have challenged the conventional view that vegetation changes are mainly driven by changing abiotic conditions. However, while this concept has been validated under natural conditions, our understanding of the long‐term consequences of plant–soil interactions for above‐belowground community assembly is restricted to mathematical and conceptual model projections. Here, we demonstrate experimentally that one‐time additions of soil biota and plant seeds alter soil‐borne nematode and plant community composition in semi‐natural grassland for 20 years. Over time, aboveground and belowground community composition became increasingly correlated, suggesting an increasing connectedness of soil biota and plants. We conclude that the initial composition of not only plant communities, but also soil communities has a long‐lasting impact on the trajectory of community assembly. 相似文献
34.
35.
Sebastian H. Grimm Berend Gagestein Jordi F. Keijzer Nora Liu Ruud H. Wijdeven Eelke B. Lenselink Adriaan W. Tuin Adrianus M.C.H. van den Nieuwendijk Gerard J.P. van Westen Constant A.A. van Boeckel Herman S. Overkleeft Jacques Neefjes Mario van der Stelt 《Bioorganic & medicinal chemistry》2019,27(5):692-699
Acute myeloid leukemia (AML) is characterized by fast progression and low survival rates, in which Fms-like tyrosine kinase 3 (FLT3) receptor mutations have been identified as a driver mutation in cancer progression in a subgroup of AML patients. Clinical trials have shown emergence of drug resistant mutants, emphasizing the ongoing need for new chemical matter to enable the treatment of this disease. Here, we present the discovery and topological structure-activity relationship (SAR) study of analogs of isoquinolinesulfonamide H-89, a well-known PKA inhibitor, as FLT3 inhibitors. Surprisingly, we found that the SAR was not consistent with the observed binding mode of H-89 in PKA. Matched molecular pair analysis resulted in the identification of highly active sub-nanomolar azaindoles as novel FLT3-inhibitors. Structure based modelling using the FLT3 crystal structure suggested an alternative, flipped binding orientation of the new inhibitors. 相似文献
36.
37.
With the increasing frequency of large‐scale restoration efforts, the need to understand the adaptive genetic structure of natural plant populations and their relation to heavily utilized cultivars is critical. Bouteloua gracilis (blue grama) is a wind‐dispersed, perennial grass consisting of several cytotypes (2n = 2×–6×) with a widespread distribution in western North America. The species is locally dominant and used regularly in restoration treatments. Using amplified fragment length polymorphism (AFLP) and cpDNA analyses, we assessed the genetic variability and adaptive genetic structure of blue grama within and among 44 sampling sites that are representative of the species’ environmental and habitat diversity in the southwestern United States. Five cultivars were also included to investigate genetic diversity and differentiation in natural versus cultivated populations. Three main findings resulted from this study: (a) Ninety‐four polymorphic AFLP markers distinguished two population clusters defined largely by samples on and off the Colorado Plateau; (b) substructure of samples on the Colorado Plateau was indicated by genetic divergence between boundary and interior regions, and was supported by cytotype distribution and cpDNA analysis; and (c) six AFLP markers were identified as “outliers,” consistent with being under selection. These loci were significantly correlated to mean annual temperature, mean annual precipitation, precipitation of driest quarter, and precipitation of wettest quarter in natural populations, but not in cultivated samples. Marker × environment relationships were found to be largely influenced by cytotype and cultivar development. Our results demonstrate that blue grama is genetically variable, and exhibits genetic structure, which is shaped, in part, by environmental variability across the Colorado Plateau. Information from our study can be used to guide the selection of seed source populations for commercial development and long‐term conservation management of B. gracilis, which could include genetic assessments of diversity and the adaptive potential of both natural and cultivated populations for wildland restoration. 相似文献
38.
39.
Victoria Cano Catalina March Jose Luis Insua Nacho Aguiló Enrique Llobet David Moranta Verónica Regueiro Gerard P. Brennan Maria Isabel Millán‐Lou Carlos Martín Junkal Garmendia José A. Bengoechea 《Cellular microbiology》2015,17(11):1537-1560
Klebsiella pneumoniae is an important cause of community‐acquired and nosocomial pneumonia. Evidence indicates that Klebsiella might be able to persist intracellularly within a vacuolar compartment. This study was designed to investigate the interaction between Klebsiella and macrophages. Engulfment of K. pneumoniae was dependent on host cytoskeleton, cell plasma membrane lipid rafts and the activation of phosphoinositide 3‐kinase (PI3K). Microscopy studies revealed that K. pneumoniae resides within a vacuolar compartment, the Klebsiella‐containing vacuole (KCV), which traffics within vacuoles associated with the endocytic pathway. In contrast to UV‐killed bacteria, the majority of live bacteria did not co‐localize with markers of the lysosomal compartment. Our data suggest that K. pneumoniae triggers a programmed cell death in macrophages displaying features of apoptosis. Our efforts to identify the mechanism(s) whereby K. pneumoniae prevents the fusion of the lysosomes to the KCV uncovered the central role of the PI3K–Akt–Rab14 axis to control the phagosome maturation. Our data revealed that the capsule is dispensable for Klebsiella intracellular survival if bacteria were not opsonized. Furthermore, the environment found by Klebsiella within the KCV triggered the down‐regulation of the expression of cps. Altogether, this study proves evidence that K. pneumoniae survives killing by macrophages by manipulating phagosome maturation that may contribute to Klebsiella pathogenesis. 相似文献
40.
Niels Andreasen Monica Simeoni Henrik Ostlund Pia I. Lisjo Tormod Fladby Amy E. Loercher Gerard J. Byrne Frances Murray Paul T. Scott-Stevens Anders Wallin Yinghua Y. Zhang Lena H. Bronge Henrik Zetterberg Agneta K. Nordberg Astrid J. Yeo Shahid A. Khan Jan Hilpert Prafull C. Mistry 《PloS one》2015,10(3)