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Myriam Baes 《Cell biochemistry and biophysics》2000,32(1-3):229-237
The gene knockout technology has been applied to generate mice lacking functional peroxisomes. These mice are a model for
Zellweger syndrome and other peroxisome biogenesis disorders that are lethal in early life. Extensive biochemical, ultrastructural,
and neurodevelopmental analyses indicate that the peroxisome deficient mice closely mimic the pathology in Zellweger patients
and will be a very useful tool to elucidate the pathogenesis of this disease. 相似文献
4.
C. K. Thoeringer U. J. Pfeiffer G. Rammes F. A. Pamplona S. Moosmang C. T. Wotjak 《Genes, Brain & Behavior》2010,9(8):947-957
Environmental factors may unleash genetically determined susceptibility to psychopathology. Great effort has been spent in identifying both the genetic basis and environmental sources of exaggerated fear in animal models of anxiety disorders. Here, we show that the origin of inbred mice, probably via subtle differences in breeding and rearing conditions, may have large consequences specifically on acquisition and retention of fear memories, while leaving anxiety‐related behaviours unaffected. These effects could be seen in BALB/cAnN (BALB), but not in C57BL/6N (C57BL/6) mice, thus suggesting their dependency on the genetic background. Increased susceptibility for developing exaggerated fear responses was accompanied by decreased long‐term depression and increased surface trafficking of the AMPA receptor GluR1 subunit at the level of the basolateral amygdala complex. Together, these data raise a novel caveat in the debate about the origins of variation in behavioural studies with experimental animals. Considering that there are currently no animal models which explicitly consider conceptual analogy to the specific gene–environment interactions observed in the aetiology of phobias, our study might suggest a novel approach and direction for further preclinical studies focusing on such aspects of phobic‐like fears. 相似文献
5.
Asymmetric and Globular Forms of AChE in Slow and Fast Muscles of 129/ReJ Normal and Dystrophic Mice 总被引:3,自引:3,他引:0
Abstract: Acetylcholinesterase activities and molecular forms were studied in normal and dystrophic 129/ReJ mice, focusing on four predominantly fast-twitch muscles and the slow-twitch soleus. The asymmetric and globular forms were analyzed separately so that the effect of dystrophy on each form could be determined. This comparative study showed the following. (1) In the normal condition, each muscle exhibited a distinct distribution of the molecular forms. (2) The diversity among the fast muscles resulted mainly from variations in the proportions of the three globular forms; in contrast, these muscles showed a constant and precise A12 /A8 /A4 ratio. (3) The slow-twitch soleus clearly differed from the other muscles in its low acetylcholinesterase activity and distinct distribution of the molecular forms, characterized by a low level of G4 and a peculiar ratio among its asymmetric forms, resulting from a relative increase of the A8 and A4 forms. (4) In dystrophic mice, the diversity of the acetylcholin esterase distribution was lost; all the fast muscles displayed profiles exhibiting the characteristics typical of the soleus. The fast-twitch extensor digitorum longus, sternomastoid, and plantaris converged towards an identical set of acetylcholinesterase molecules. (5) In contrast, the acetylcholinesterase activity and molecular forms of the soleus were only slightly affected by the disease. These results reveal that the dystrophy modifies both categories of molecular forms of acetylcholinesterase in a very precise manner. Such complex changes, which are highly reproducible in a variety of different muscles, are unlikely to result from nonspecific reactions secondary to the disease. 相似文献
6.
Jan A. Gossen Wiljo J. F. de Leeuw Aart Verwest Paul H. M. Lohman Jan Vijg 《Mutation research》1991,250(1-2):423-429
To study spontaneous and induced mutagenesis in vivo we recently constructed a series of transgenic mice harboring different numbers of bacteriophage lambda shuttle vectors, provided with a LacZ mutational target gene, integrated in their genome. The transgenic mice enabled analysis of spontaneous and induced mutation frequencies in postmitotic tissues like liver and brain. The obtained data indicated spontaneous mutation frequencies in the order of −5 - 10−6. Here we report a 25–100 times higher spontaneous mutation frequency in liver and brain DNA of mice from strain 35.5, with the lambda-gt10LacZ concatemer integrated on the X-chromosome. These results indicate the presence of a mutational ‘hot spot’ in the mammalian somatic genome in vivo. 相似文献
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B. Kopmels J. Mariani N. Delhaye-Bouchaud F. Audibert D. Fradelizi E. E. Wollman 《Journal of neurochemistry》1992,58(1):192-199
We recently reported an abnormal production of interleukin-1 (IL-1) in peripheral macrophages of several neurological mutant mice that exhibit patterns of neuronal degeneration, especially in the cerebellum. After in vitro activation by lipopolysaccharide acid (LPS), these macrophages hyperexpress IL-1 beta mRNA and hyperproduce IL-1 protein in comparison with +/+ controls. In the present study, focused on the staggerer mutant mice, we investigate if this genetic dysregulation is specific for IL-1 beta or if it reflects a generalized hyperexcitability of these macrophages. The hyperexpression of IL-1 beta mRNA in sg/sg macrophages is present whatever the duration of LPS stimulation, even for periods as short as 15 min, although it reaches a maximum after 4 h of stimulation. The hyperinducibility of sg/sg macrophages is observed even when very low doses of LPS are used (0.01 microgram/ml) and reaches its maximum for 5 micrograms/ml LPS. Synthetic molecules (muramyl dipeptides), such as N-acetylmuramyl-L-alanyl-D-isoglutamine or murabutide, known as macrophage activators, are also efficient in revealing the cytokine hyperexpression in sg/sg macrophages. In addition, hyperexpression of two other cytokines, i.e., tumor necrosis factor-alpha and IL-1 alpha mRNAs, is also detected in LPS-stimulated macrophages of mutant mice. Finally, the effect of an inhibitor of protein synthesis, cycloheximide, is similar in +/+ and sg/sg macrophages. As a whole, these data lead us to conclude that the sg/sg macrophages are in a state of general hyperexcitability when compared with +/+ ones. 相似文献
9.
Elucidation of the pathogenesis in respiratory chain diseases is of great importance for developing specific treatments. The limitations inherent to the use of patient material make studies of human tissues often difficult and the mouse has therefore emerged as a suitable model organism for studies of respiratory chain diseases. In this review, we present an overview of the field and discuss in depth a few examples of animal models reproducing pathology of human disease with primary and secondary respiratory chain involvement. 相似文献
10.
The existence of long-lasting (15–18 h) alterations of neurotrasmitter amino acid levels following a single or repeated acoustic stimulations in audiogenic seizure-prone Rb1 and Rb2 mice and suizure-resistant Rb3 mice were investigated. The levels of glutamate, aspartate, glycine, taurine, and of some of their precursors: glutamine and serine were determined. Fourteen brain areas were examined. Alterations were found only in 6 brain areas (pons, olfactory bulbs, superior colliculus, inferior colliculus, olfactory tubercles and raphe). Most frequent occuring changes were observed in pons and olfactory tubercles. These changes concerned mainly the excitatory amino acids, glutamate, and aspartate. Alterations of taurine, glycine and serine were also recorded.Abbreviations GABA
4-aminobutyrate
- Tau
taurine
- Gly
glycine
- Asp
aspertate
- Glu
glutamate
- Gln
glutamine
- Ser
serine
- OB
olfactory bulbs
- OT
olfactory tubercles
- Sr
striatum
- Se
septum
- Hy
hypothalamus
- Th
thalamus
- Hi
hippocampus
- A
amygdala
- SC
superior colliculus
- IC
inferior colliculus
- FC
frontal cortex
- C
cerebellum
- P
pons medulla
- Ra
raphe
- AA
neurotransmitter amino acids
- I
inhibitory
- E
excitatory
- SSL
steady-state level
Plesant memories of Lawrence Austin's sojourn in my group at Strasbourg gather upon me when I dedicate this article on this occasion for the contribution that Lawrence Austin has made for the cause of neurochemical researchers. 相似文献