首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   3290篇
  免费   135篇
  国内免费   1篇
  3426篇
  2022年   16篇
  2021年   25篇
  2020年   13篇
  2019年   32篇
  2018年   35篇
  2017年   29篇
  2016年   49篇
  2015年   82篇
  2014年   110篇
  2013年   265篇
  2012年   185篇
  2011年   203篇
  2010年   129篇
  2009年   129篇
  2008年   202篇
  2007年   179篇
  2006年   169篇
  2005年   175篇
  2004年   174篇
  2003年   176篇
  2002年   177篇
  2001年   46篇
  2000年   53篇
  1999年   61篇
  1998年   50篇
  1997年   51篇
  1996年   44篇
  1995年   37篇
  1994年   23篇
  1993年   39篇
  1992年   45篇
  1991年   33篇
  1990年   22篇
  1989年   31篇
  1988年   32篇
  1987年   40篇
  1986年   25篇
  1985年   23篇
  1984年   21篇
  1983年   33篇
  1982年   21篇
  1981年   14篇
  1980年   18篇
  1979年   9篇
  1978年   11篇
  1977年   13篇
  1976年   8篇
  1975年   8篇
  1974年   9篇
  1973年   11篇
排序方式: 共有3426条查询结果,搜索用时 15 毫秒
1.
Glycine receptors (GlyRs) play important roles in regulating hippocampal neural network activity and spinal nociception. Here we show that, in cultured rat hippocampal (HIP) and spinal dorsal horn (SDH) neurons, 17-β-estradiol (E2) rapidly and reversibly reduced the peak amplitude of whole-cell glycine-activated currents (I Gly). In outside-out membrane patches from HIP neurons devoid of nuclei, E2 similarly inhibited I Gly, suggesting a non-genomic characteristic. Moreover, the E2 effect on I Gly persisted in the presence of the calcium chelator BAPTA, the protein kinase inhibitor staurosporine, the classical ER (i.e. ERα and ERβ) antagonist tamoxifen, or the G-protein modulators, favoring a direct action of E2 on GlyRs. In HEK293 cells expressing various combinations of GlyR subunits, E2 only affected the I Gly in cells expressing α2, α2β or α3β subunits, suggesting that either α2-containing or α3β-GlyRs mediate the E2 effect observed in neurons. Furthermore, E2 inhibited the GlyR-mediated tonic current in pyramidal neurons of HIP CA1 region, where abundant GlyR α2 subunit is expressed. We suggest that the neuronal GlyR is a novel molecular target of E2 which directly inhibits the function of GlyRs in the HIP and SDH regions. This finding may shed new light on premenstrual dysphoric disorder and the gender differences in pain sensation at the CNS level.  相似文献   
2.

Objective

A novel filamentous cyanobacterium, a photosynthesizing microorganism, was isolated from a river, and its unique features of flocculation and pentadecane production were characterized.

Results

Microscopic observations and a phylogenetic analysis with 16S rDNA revealed that this strain was a Limnothrix species denoted as the SK1-2-1 strain. Auto cell-flocculation was observed when this strain was exposed to a two-step incubation involving a standing cultivation following a shaking preincubation. Flocculation was enhanced by blue light at a wavelength at 470 nm and irradiation for several hours to 1 day. Moreover, the strain exhibiting exponential cell growth may preferentially accumulate alkanes as pentadecane C15H32 alkane, which may be used as jet fuel, at a range of approximately 1% in the dry cell weight of flocculated cells.

Conclusion

This is the first study on biofuel production using flocculated cells in which the specific manner of production may be regulated by cultivation conditions.
  相似文献   
3.
The evolution of exclusive male parental care is a major and controversial issue in behavioural ecology. Although arthropods practicing paternal care are thought to be key taxa for investigating this issue, few studies have attempted to clarify the selection factors associated with male behaviour and fitness consequences in arthropods. In the millipede Brachycybe nodulosa, males curl their bodies around egg masses on the undersides of decaying logs. Male‐removal experiments in the laboratory strongly suggest that males defend the eggs against fungal infection. Orphaned eggs were soon covered by hyphae and no eggs hatched, whereas almost all eggs brooded by males successfully hatched. The egg‐brooding males showed no aggressive responses when disturbed. Only some mature males bred in the field. Furthermore, the number of eggs brooded varied greatly among the males. Selected generalized linear models revealed that males with a wide seventh body segment, which possesses gonopods (genital legs), tended to succeed in brooding; and males with a wider body also obtained more eggs. Colony attributes had no significant effects on male brooding. We discuss the possible sexual selection mechanisms that could accomplish this pattern of brooding success among male B. nodulosa.  相似文献   
4.
The mechanism of microsomal oxidative deamination of alicyclic primary amines: cyclopentylamine, cyclohexylamine, cycloheptylamine, 1- and 2-aminoindan, 1- and 2-aminotetralin, was studied under an atmosphere of 18O2 or in a medium containing H218O. The oxygen-18 contents of the products determined by gas-liquid chromatography/mass spectrometry revealed that almost all (75–100 atom%) of the oxygen of oximes was derived from molecular oxygen, whereas a part (4–25 atom% ) of the oxygen of ketones. The studies on the hydrolysis of oximes and the oxygen exchange reaction of ketones proved that the latter proceeded at a considerable rate (t12 = 9.5–336 min) and the former made a minor contribution, to explain why the major portion (75–96 atom%) of the oxygen in ketones was derived from water. The results support the mechanism that microsomal deamination proceeds mainly through a carbinolamine intermediate, which is initially hydroxylated at the α carbon to the amino group, partially equilibrating with the imine, and then rearranges to form a ketone and ammonia.  相似文献   
5.
Botulinum neurotoxins (BoNTs) are among the most poisonous biological substances known. They assemble with non-toxic non-hemagglutinin (NTNHA) protein to form the minimally functional progenitor toxin complexes (M-PTC), which protects BoNT in the gastrointestinal tract and releases it upon entry into the circulation. Here we provide molecular insight into the assembly between BoNT/A and NTNHA-A using small-angle X-ray scattering. We found that the free form BoNT/A maintains a pH-independent conformation with limited domain flexibility. Intriguingly, the free form NTNHA-A adopts pH-dependent conformational changes due to a torsional motion of its C-terminal domain. Once forming a complex at acidic pH, they each adopt a stable conformation that is similar to that observed in the crystal structure of the M-PTC. Our results suggest that assembly of the M-PTC depends on the environmental pH and that the complex form of BoNT/A is induced by interacting with NTNHA-A at acidic pH.  相似文献   
6.
We evaluated the effect of carotenoids on the dinitrofluorobenzene (DNFB)-induced contact hypersensitivity in mice. Dietary carotenoids significantly inhibited ear swelling and reduced the contents of TNF-α and histamine in the DNFB-treated mice. Our results suggest that dietary carotenoids exerted an anti-inflammatory effect by suppressing mast cell degranulation in vivo.  相似文献   
7.
Yeast extract-iron-gluconic acid-dihydroxyacetone-serum medium that allows axenic cultivation of Entamoeba dispar was designed based on casein-free yeast extract-iron-serum (YI-S) medium, and the usefulness of the medium was assessed. The main differences from YI-S medium are replacement of glucose by gluconic acid, addition of dihydroxyacetone and D-galacturonic acid monohydrate, and sterilization by filtration. This medium promoted the axenic growth of 5 strains of E. dispar (2 strains of nonhuman primate isolates and 3 strains of human isolates). In addition, to clarify the biological basis for the growth of E. dispar in this medium, analyses of relevant enzymes on the glycolytic pathway of the amoebae as well as of the protozoans that are the best culture supplement for amoebae are being performed.  相似文献   
8.
Specific peptidyl linkers that result in the heterodimerization of functional proteins, which is catalyzed by microbial transglutaminase from Streptomyces mobaraensis (MTG), were generated based on a ribonuclease S-peptide using site-directed mutagenesis. The peptidyl linkers designated as Lys-tag and Gln-tag were designed to possess sole reactive Lys or Gln residue that was amenable for selective Lys-Gln cross-linkage of different proteins. Green fluorescent protein variants, ECFP and EYFP, were employed as model proteins, and those Lys- and Gln-tags were fused to the N-termini of ECFP and EYFP, respectively. As a result, we succeeded in solely obtaining the ECFP-EYFP heterodimer without forming multiply cross-linked byproducts. It was found that the reactivity of peptidyl linkers varied according to the type of amino acid to be replaced. Peptidyl linkers with a basic amino acid (Arg) exhibited the highest reactivity in the cross-linking reaction, suggesting the cationic residue substrate preference of MTG. Kinetic analysis utilizing fluorescent resonance energy transfer (FRET), that is only observed upon the heterodimeric ECFP-EYFP conjugation, revealed that the amino acid replacement contributed to the acceleration of cross-linking reactions by increasing catalytic turnover (k(cat)), rather than substrate binding affinity (K(m)). Finally, using a ribonuclease S-protein, the manipulation of enzymatic protein cross-linking based on specific S-peptide:S-protein interactions was explored. Since newly designed Lys- and Gln-tags retained binding affinities to the S-protein, the heterodimerization was perfectly restrained by wrapping them with the S-protein. The results suggest the possibility of limited protein conjugation by tuning steric hindrance against the MTG. Tailoring enzymatic posttranslational modifications with either engineering peptidyl substrates or by taking specific peptide-protein interactions into consideration may facilitate the development of a new sequential protein conjugation method for the preparation of multifunctional protein.  相似文献   
9.
Landscape and Ecological Engineering - Investigating factors underlying human-wildlife conflicts in agricultural landscapes is important for both preventing crop damage and wildlife conservation....  相似文献   
10.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号