全文获取类型
收费全文 | 772篇 |
免费 | 66篇 |
专业分类
838篇 |
出版年
2021年 | 10篇 |
2018年 | 12篇 |
2016年 | 10篇 |
2015年 | 18篇 |
2014年 | 23篇 |
2013年 | 32篇 |
2012年 | 38篇 |
2011年 | 36篇 |
2010年 | 19篇 |
2009年 | 22篇 |
2008年 | 30篇 |
2007年 | 34篇 |
2006年 | 20篇 |
2005年 | 34篇 |
2004年 | 25篇 |
2003年 | 28篇 |
2002年 | 25篇 |
2001年 | 20篇 |
2000年 | 22篇 |
1999年 | 25篇 |
1998年 | 7篇 |
1997年 | 6篇 |
1996年 | 6篇 |
1995年 | 10篇 |
1994年 | 8篇 |
1993年 | 8篇 |
1992年 | 13篇 |
1991年 | 14篇 |
1990年 | 15篇 |
1989年 | 14篇 |
1988年 | 15篇 |
1987年 | 21篇 |
1986年 | 14篇 |
1985年 | 6篇 |
1984年 | 16篇 |
1983年 | 10篇 |
1982年 | 12篇 |
1981年 | 5篇 |
1980年 | 12篇 |
1979年 | 18篇 |
1978年 | 9篇 |
1977年 | 11篇 |
1976年 | 12篇 |
1975年 | 8篇 |
1974年 | 9篇 |
1973年 | 6篇 |
1972年 | 10篇 |
1971年 | 8篇 |
1969年 | 5篇 |
1968年 | 8篇 |
排序方式: 共有838条查询结果,搜索用时 0 毫秒
101.
Summary The reaction rate of glucose-6-phosphate dehydrogenase activity in liver sections from fed and starved rats has been monitored by the continuous measurement at 37 C of the reaction product as it is formed using scanning and integrating microdensitometry. Control media lacked either substrate or both substrate and coenzyme. All reactions were nonlinear; however, subtraction of either of the controls from the test response produced linearity. Differing responses in sections of livers from fed and fasted rats indicate that the appropriate control medium for use in the assay of this dehydrogenase is one lacking both substrate and coenzyme rather than a medium containing coenzyme. The reaction rate was the same with each of the final acceptors. Problems with the diffusion of the formazan of BPST and with the failure to precipitate the formazan of Neotetrazolium make Tetranitro BT and Nitro BT the tetrazolium salts of choice in quantitative dehydrogenase assays. 相似文献
102.
C McBerry CE Egan R Rani Y Yang D Wu N Boespflug L Boon B Butcher J Mirpuri SP Hogan EY Denkers J Aliberti DR Herbert 《Journal of immunology (Baltimore, Md. : 1950)》2012,189(6):3078-3084
IL-12-mediated type 1 inflammation confers host protection against the parasitic protozoan Toxoplasma gondii. However, production of IFN-γ, another type 1 inflammatory cytokine, also drives lethality from excessive injury to the intestinal epithelium. As mechanisms that restore epithelial barrier function following infection remain poorly understood, this study investigated the role of trefoil factor 2 (TFF2), a well-established regulator of mucosal tissue repair. Paradoxically, TFF2 antagonized IL-12 release from dendritic cells (DCs) and macrophages, which protected TFF2-deficient (TFF2(-/-)) mice from T. gondii pathogenesis. Dysregulated intestinal homeostasis in naive TFF2(-/-) mice correlated with increased IL-12/23p40 levels and enhanced T cell recruitment at baseline. Infected TFF2(-/-) mice displayed low rates of parasite replication and reduced gut immunopathology, whereas wild-type (WT) mice experienced disseminated infection and lethal ileitis. p38 MAPK activation and IL-12p70 production was more robust from TFF2(-/-)CD8(+) DC compared with WT CD8(+) DC and treatment of WT DC with rTFF2 suppressed TLR-induced IL-12/23p40 production. Neutralization of IFN-γ and IL-12 in TFF2(-/-) animals abrogated resistance shown by enhanced parasite replication and infection-induced morbidity. Hence, TFF2 regulated intestinal barrier function and type 1 cytokine release from myeloid phagocytes, which dictated the outcome of oral T. gondii infection in mice. 相似文献
103.
Salgado PS Makeyev EV Butcher SJ Bamford DH Stuart DI Grimes JM 《Structure (London, England : 1993)》2004,12(2):307-316
The RNA-dependent RNA polymerase of bacteriophage phi6 transcribes mRNA from the three segments of the dsRNA viral genome. We have cocrystallized RNA oligonucleotides with the polymerase, revealing the mode of binding of RNA templates. This binding is somewhat different from that previously seen for DNA oligomers, leading to additional RNA-protein hydrogen bonds, consistent with a preference for RNA. Activation of the RNA/polymerase complex by the addition of substrate and Mg2+ initiates a single round of reaction within the crystal to form a dead-end complex that partially collapses within the enzyme active site. By replacing Mg2+ with Ca2+, we have been able to capture the inhibited complex which shows distortion that explains the structural basis for the inhibition of such polymerases by Ca2+. 相似文献
104.
In response to high population density or low food supply, the nematode Caenorhabditis elegans enters an alternative larval stage, known as the dauer, that can withstand adverse conditions for prolonged periods. C. elegans senses its population density through a small-molecule signal, traditionally called the dauer pheromone, that it secretes into its surroundings. Here we show that the dauer pheromone consists of several structurally related ascarosides-derivatives of the dideoxysugar ascarylose-and that two of these ascarosides (1 and 2) are roughly two orders of magnitude more potent at inducing dauer formation than a previously reported dauer pheromone component (3) and constitute a physiologically relevant signal. The identification of dauer pheromone components 1 and 2 will facilitate the identification of target receptors and downstream signaling proteins. 相似文献
105.
The reactions of N,N-dimethylaminopropyl chalcogenolates with platinum(II) compounds have been carried out and complexes of the types [PtCl(ECH2CH2CH2NMe2)]2 (1) (E = S (1a) and Se (1b)), [Pt(ECH2CH2CH2NMe2)2]n (2) (E = S (2a) and Se (2b)), [(PtCl2)2{(Me2NCH2CH2CH2E)2}]n (3), [PtX(SeCH2CH2CH2NMe2)]2 (4) (X = SePh (4a) and OAc (4b)) and [PtCl(ECH2CH2CH2NMe2)(PR3)]n (5) (E = S, Se, Te) have been isolated. These complexes have been characterized by elemental analysis, IR, UV-Vis, NMR (1H, 13C, 31P, 77Se, 195Pt) spectroscopy and FAB mass spectral data. The structures of [PtCl(SeCH2CH2CH2NMe2)]2 (1b) and [PtCl(SCH2CH2CH2NMe2)(PPr3)]2 (5a) have been established by single crystal X-ray diffraction data. Both the molecules have dimeric structures. In 1b, two platinum atoms are held together by symmetrically bridging Se atoms of the chelating selenolate groups. In 5a, two thiolates form a four-membered Pt2S2 bridge with dangling NMe2 groups. 相似文献
106.
Dendritic cells support sequential reprogramming of chemoattractant receptor profiles during naive to effector T cell differentiation 总被引:8,自引:0,他引:8
T cells undergo chemokine receptor switches during activation and differentiation in secondary lymphoid tissues. Here we present evidence that dendritic cells can induce changes in T cell expression of chemokine receptors in two continuous steps. In the first switch over a 4-5 day period, dendritic cells up-regulate T cell expression of CXCR3 and CXCR5. Additional stimulation leads to the second switch: down-regulation of lymphoid tissue homing related CCR7 and CXCR5, and up-regulation of Th1/2 effector tissue-targeting chemoattractant receptors such as CCR4, CCR5, CXCR6, and CRTH2. We show that IL-4 and IL-12 can determine the fate of the secondary chemokine receptor switch. IL-4 enhances the generation of CCR4(+) and CRTH2(+) T cells, and suppresses the generation of CXCR3(+) T cells and CCR7(-) T cells, while IL-12 suppresses the level of CCR4 in responding T cells. Furthermore, IL-4 has positive effects on generation of CXCR5(+) and CCR7(+) T cells during the second switch. Our study suggests that the sequential switches in chemokine receptor expression occur during naive T cell interaction with dendritic cells. The first switch of T cell chemokine receptor expression is consistent with the fact that activated T cells migrate within lymphoid tissues for interaction with B and dendritic cells, while the second switch predicts the trafficking behavior of effector T cells away from lymphoid tissues to effector tissue sites. 相似文献
107.
One field and 3 aquaria experiments were done to quantify the short-term mortality of yellowfin bream Acanthopagrus australis and mulloway Argyrosomus japonicus after being angled and subjected to 3 general handling treatments. Anglers were supplied with identical J-type hooks and asked to handle hooked fish by either (1) physically removing the hook or (2) cutting the line (5 cm from the mouth of the fish) and leaving the hook in. Some hooked A. japonicus were subjected to a third handling treatment where the line was cut underwater without exposing the fish to air. Technical and biological data were collected before all fish were released into sea cages and monitored for 5 d. Control fish were seined and similarly caged and monitored. Concentrations of plasma glucose and cortisol were collected from a sample of fish on the first and last day of the experiments. Significant predictors of mortality for both species involved the presence of blood at the mouth and an interaction between anatomical hook location and hook removal. A. australis and A. japonicus that had their ingested hooks removed experienced the greatest mortalities (87.5 and 72.7%, respectively). Typically, these fish suffered damage to their oesophagus, stomach wall and vital organs. Mortality rates of A. australis and A. japonicus were significantly decreased to 1.7 and 16%, respectively, when they were released with their lines cut, with some of these fish free of hooks after 5 d. In contrast, few mortalities occurred in either species when the hooks were removed or the lines cut on mouth-hooked fish or in A. japonicus when it was released with no air exposure. For A. australis, the field- and aquaria-based experiments provided comparable results in terms of identifying treatment-specific effects, but there were potential biases in rates of hook ingestion. Irrespective of the treatment of fish, all experiments caused physiological changes measured as elevations in either plasma cortisol or glucose. We concluded that anglers should cut the line from hook-ingested A. australis and A. japonicus, but remove the hook from mouth-hooked individuals to prevent subsequent ingestion. Further research is required to examine the longer-term consequences of these handling practices on fish health. 相似文献
108.
Age and growth of mangrove red snapper Lutjanus argentimaculatus at its cool‐water‐range limits 下载免费PDF全文
T. P. Piddocke G. L. Butler P. A. Butcher J. Stewart D. J. Bucher L. Christidis 《Journal of fish biology》2015,86(5):1587-1600
This study investigates the age and growth of Lutjanus argentimaculatus at its southern (cooler) range limits in eastern Australia. Specimens were collected from New South Wales and southern Queensland between November 2011 and December 2013. Fork lengths (LF) ranged from 190 to 1019 mm, and ages ranged from 2+ to 57+ years. Growth was described by the von Bertalanffy growth function with coefficients L∞ = 874·92 mm, K = 0·087 year?1 and t0 = ?2·76 years. Estimates of the instantaneous natural mortality rate (M) ranged from 0·072 to 0·25. The LF (mm) and mass (W; g) relationship was represented by the equation: . The maximum age of 57+ years is the oldest reported for any lutjanid and comparisons with tropical studies suggest that the age‐based demography of L. argentimaculatus follows a latitudinal gradient. High maximum ages and low natural mortality rates indicate considerable vulnerability to overexploitation at the species' cool‐water‐range limits. These results demonstrate the need to identify underlying processes driving latitudinal gradients in fish demography. 相似文献
109.
Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from Drosophila, mice, and humans 总被引:10,自引:3,他引:10
Recent studies of mitochondrial DNA (mtDNA) variation in mammals and
Drosophila have shown an excess of amino acid variation within species
(replacement polymorphism) relative to the number of silent and replacement
differences fixed between species. To examine further this pattern of
nonneutral mtDNA evolution, we present sequence data for the ND3 and ND5
genes from 59 lines of Drosophila melanogaster and 29 lines of D. simulans.
Of interest are the frequency spectra of silent and replacement
polymorphisms, and potential variation among genes and taxa in the
departures from neutral expectations. The Drosophila ND3 and ND5 data show
no significant excess of replacement polymorphism using the
McDonald-Kreitman test. These data are in contrast to significant
departures from neutrality for the ND3 gene in mammals and other genes in
Drosophila mtDNA (cytochrome b and ATPase 6). Pooled across genes, however,
both Drosophila and human mtDNA show very significant excesses of amino
acid polymorphism. Silent polymorphisms at ND5 show a significantly higher
variance in frequency than replacement polymorphisms, and the latter show a
significant skew toward low frequencies (Tajima's D = -1.954). These
patterns are interpreted in light of the nearly neutral theory where mildly
deleterious amino acid haplotypes are observed as ephemeral variants within
species but do not contribute to divergence. The patterns of polymorphism
and divergence at charge-altering amino acid sites are presented for the
Drosophila ND5 gene to examine the evolution of functionally distinct
mutations. Excess charge-altering polymorphism is observed at the carboxyl
terminal and excess charge-altering divergence is detected at the amino
terminal. While the mildly deleterious model fits as a net effect in the
evolution of nonrecombining mitochondrial genomes, these data suggest that
opposing evolutionary pressures may act on different regions of
mitochondrial genes and genomes.
相似文献
110.
Vibhor Kumar Sarah J. Butcher Katariina ??rni Peter Engelhardt Jukka Heikkonen Kimmo Kaski Mika Ala-Korpela Petri T. Kovanen 《PloS one》2011,6(5)