全文获取类型
收费全文 | 3870篇 |
免费 | 348篇 |
国内免费 | 2篇 |
专业分类
4220篇 |
出版年
2022年 | 37篇 |
2021年 | 62篇 |
2020年 | 27篇 |
2019年 | 46篇 |
2018年 | 58篇 |
2017年 | 44篇 |
2016年 | 79篇 |
2015年 | 120篇 |
2014年 | 149篇 |
2013年 | 164篇 |
2012年 | 204篇 |
2011年 | 209篇 |
2010年 | 112篇 |
2009年 | 107篇 |
2008年 | 152篇 |
2007年 | 150篇 |
2006年 | 156篇 |
2005年 | 109篇 |
2004年 | 133篇 |
2003年 | 115篇 |
2002年 | 107篇 |
2001年 | 79篇 |
2000年 | 77篇 |
1999年 | 72篇 |
1998年 | 32篇 |
1997年 | 36篇 |
1992年 | 75篇 |
1991年 | 72篇 |
1990年 | 79篇 |
1989年 | 88篇 |
1988年 | 83篇 |
1987年 | 80篇 |
1986年 | 75篇 |
1985年 | 65篇 |
1984年 | 45篇 |
1983年 | 57篇 |
1982年 | 36篇 |
1981年 | 47篇 |
1980年 | 50篇 |
1979年 | 67篇 |
1978年 | 77篇 |
1977年 | 45篇 |
1976年 | 42篇 |
1975年 | 38篇 |
1974年 | 58篇 |
1973年 | 46篇 |
1971年 | 35篇 |
1970年 | 32篇 |
1969年 | 32篇 |
1967年 | 29篇 |
排序方式: 共有4220条查询结果,搜索用时 15 毫秒
81.
Manuel Sanchez-Fernandez George M. Katz Guilherme Suarez-Kurtz Gregory J. Kaczorowski John P. Reuben 《The Journal of membrane biology》1993,135(3):273-287
The known action of uridine triphosphate (UTP) to contract some types of vascular smooth muscle, and the present finding that it is more potent than adenosine triphosphate in eliciting an increase in cytosolic Ca2+ concentration in aortic smooth muscle, led us to investigate the mode of action of this nucleotide. With this aim, cultured bovine aorta cells were subjected to patch-clamp methodologies under various conditions. Nucleotide-induced variations in cytosolic Ca2+ were monitored by using single channel recordings of the high conductance Ca2+-activated K+ (Maxi-K) channel within on-cell patches as a reporter, and whole-cell currents were measured following perforation of the patch. In cells bathed in Na+-saline, UTP (>30 nm) induced an inward current, and both Maxi-K channel activity and unitary current amplitude of the Maxi-K channel transiently increased. Repetitive exposures elicited similar responses when 5 to 10 min wash intervals were allowed between challenges of nucleotide. Oscillations in channel activity, but not oscillation in current amplitude were frequently observed with UTP levels > 0.1 m. Cells bathed in K+ saline (150
m) were less sensitive to UTP (5-fold), and did not show an increase in unitary Maxi-K current amplitude. Since the increase in amplitude occurs due to depolarization of the cell membrane, a change in amplitude was not observed in cells previously depolarized with K+ saline. The enhancement of Maxi-K channel activity in the presence of UTP was not diminished by Ca2+ entry blockers or by removal of extracellular Ca2+. However, in the latter case, repetitive responses progressively declined. These observations, as well as data comparing the action of low concentrations of Ca2+ ionophores (<5 m) to that of UTP indicate that both agents elevate cytosolic Ca2+ by mobilization of this ion from intracellular pools. However, the Ca2+ ionophore did not cause membrane depolarization, and thus did not change unitary current amplitude. The effect of UTP on Maxi-K channel activity and current amplitude was blocked by pertussis toxin and by phorbol 12-myristate 13-acetate (PMA), but was not modified by okadaic acid, or by inhibitors of protein kinase C (PKC). Our data support a model in which a pyrimidinergic receptor is coupled to a G protein, and this interaction mediates release of Ca2+ from intracellular pools, presumably via the phosphatidyl inositol pathway. This also results in activation of membrane channels that give rise to an inward current and depolarization. Ultimately, smooth muscle contraction ensues. PKC does not appear to be directly involved, even though the UTP response is blocked by low nm levels of PMA. While the latter data implicate PKC in diminishing the UTP response, agents that inhibit either PKC or phosphatase activity did not prevent abolition of UTP responses by PMA, nor did they modify basal channel activity. 相似文献
82.
Jérémy Gauthier Joana Meier Fabrice Legeai Melanie McClure Annabel Whibley Anthony Bretaudeau Hélène Boulain Hugues Parrinello Sam T. Mugford Richard Durbin Chenxi Zhou Shane McCarthy Christopher W. Wheat Florence Piron-Prunier Christelle Monsempes Marie-Christine François Paul Jay Camille Noûs Emma Persyn Emmanuelle Jacquin-Joly Camille Meslin Nicolas Montagné Claire Lemaitre Marianne Elias 《Molecular ecology resources》2023,23(4):872-885
The ithomiine butterflies (Nymphalidae: Danainae) represent the largest known radiation of Müllerian mimetic butterflies. They dominate by number the mimetic butterfly communities, which include species such as the iconic neotropical Heliconius genus. Recent studies on the ecology and genetics of speciation in Ithomiini have suggested that sexual pheromones, colour pattern and perhaps hostplant could drive reproductive isolation. However, no reference genome was available for Ithomiini, which has hindered further exploration on the genetic architecture of these candidate traits, and more generally on the genomic patterns of divergence. Here, we generated high-quality, chromosome-scale genome assemblies for two Melinaea species, M. marsaeus and M. menophilus, and a draft genome of the species Ithomia salapia. We obtained genomes with a size ranging from 396 to 503 Mb across the three species and scaffold N50 of 40.5 and 23.2 Mb for the two chromosome-scale assemblies. Using collinearity analyses we identified massive rearrangements between the two closely related Melinaea species. An annotation of transposable elements and gene content was performed, as well as a specialist annotation to target chemosensory genes, which is crucial for host plant detection and mate recognition in mimetic species. A comparative genomic approach revealed independent gene expansions in ithomiines and particularly in gustatory receptor genes. These first three genomes of ithomiine mimetic butterflies constitute a valuable addition and a welcome comparison to existing biological models such as Heliconius, and will enable further understanding of the mechanisms of adaptation in butterflies. 相似文献
83.
Maxim K. Elias 《Pal?ontologische Zeitschrift》1962,36(1):29-37
The type specimen ofGonioloboceras goniolobum (Meek), rediscovered by Spath in the British Museum, is the foundation for a more accurate comparative study of this and other species ofGonioloboceras.Gonioloboceras described asG. goniolobum byElias in 1938 is differentiated asGonioloboceras schmidti, new species. Suture sets (new term) for several growth stages inG. goniolobum (Meek),G. welleriSmith,G. schmidtiElias, G.eliasiMiller &Owen, andG. asiaticumLibrovitch are assembled and used for differentiation of the species.The Kazakhstan goniatite faunule containingG. asiaticum is considered of very late Pennsylvanian age. 相似文献
84.
An absorbable catheter for use in regional anticoagulation in microvascular and peripheral vascular surgery was studied in 20 sites in 10 adult beagle dogs to answer three questions: (1) Could the polyglycolic acid and trimethylene carbonate catheter withstand intraarterial pressures of infusion and completely absorb over a predictable time interval? (2) Could the catheter be filled with heparin and maintain patency for reuse after a 24-hour interval? (3) Could the catheter be placed in a side branch of a major artery and, after catheter dissolution, maintain long-term patency of the primary feeding artery? The catheters were completely absorbed from 24 to 34 weeks following implantation. The catheters were able to withstand intraarterial pressures, and no evidence of significant thrombosis of the primary feeding artery was seen in any animal studied. No complications of catheter leak, hematoma formation within the catheter placement sites, or sepsis were noted in any of the 20 catheter sites studied. 相似文献
85.
A. Gough S. Chapman K. Wagstaff P. Emery E. Elias 《BMJ (Clinical research ed.)》1996,312(7024):169-172
Monocycline is the most widely prescribed systemic antibiotic for acne largely because it needs to be given only once or twice a day and seems not to induce resistance. Up to April 1994 11 cases of minocycline induced systemic lupus erythematosus and 16 cases of hepatitis had been reported to the Committee on Safety of Medicines. An analysis of these cases together with seven other cases shows the severity of some of these reactions. Two patients died while taking the drug for acne and a further patient needed a liver transplant. Acne itself can induce arthritis and is often seen in association with autoimmine liver disease, but the clinical and biochemical resolution seen after withdrawal of the drug, despite deterioration of the acne, suggests a drug reaction. In five cases re-exposure led to recurrence. Because reactions may be severe early recognition is important to aid recovery and also to avoid invasive investigations and treatments such as corticosteroids and immunosuppresants. Safer alternatives should be considered for treating acne. 相似文献
86.
P Zhong S D Pratt R P Edalji K A Walter T F Holzman A G Shivakumar L Katz 《Journal of bacteriology》1995,177(15):4327-4332
ErmC' is a methyltransferase that confers resistance to the macrolide-lincosamide-streptogramin B group of antibiotics by catalyzing the methylation of 23S rRNA at a specific adenine residue (A-2085 in Bacillus subtilis; A-2058 in Escherichia coli). The gene for ErmC' was cloned and expressed to a high level in E. coli, and the protein was purified to virtual homogeneity. Studies of substrate requirements of ErmC' have shown that a 262-nucleotide RNA fragment within domain V of B. subtilis 23S rRNA can be utilized efficiently as a substrate for methylation at A-2085. Kinetic studies of the monomethylation reaction showed that the apparent Km of this 262-nucleotide RNA oligonucleotide was 26-fold greater than the value determined for full-size and domain V 23S rRNA. In addition, the Vmax for this fragment also rose sevenfold. A model of RNA-ErmC' interaction involving multiple binding sites is proposed from the kinetic data presented. 相似文献
87.
The regulation of the voltage-activated chloride current conductance (G
Cl
) in toad skin was investigated by the use of the SH reagents N-ethylmaleimide (NEM) and p-chloro-mercuricbenzenesulfonic
acid PCMBS. This anion pathway is controlled by a voltage-sensitive gating regulator. Mucosal application of NEM decreased
the voltage-activation in a time and concentration dependent manner, half-maximal inhibition being exerted at a concentration
of 30 μm within 20 min. At concentrations higher than 100 μm, the voltage-activated G
Cl
was near-completely and irreversibly inhibited in less than 10 min. Resting, deactivated conductance was essentially unaffected.
NEM had no effect on active sodium transport (measured as I
sc
) under conditions, which fully dissipated the voltage-activated G
Cl
. After complete inhibition of the voltage-activated G
Cl
with NEM, chloride conductance could still be stimulated by CPT-cAMP as in control tissues. Under these conditions, NEM at
concentrations above 1 mm decreased G
Cl
reversibly. Mucosal application of PCMBS at 500 μm inhibited the activated conductance by 35%, which was slightly reversible. Inhibition of voltage-activated G
Cl
, which was observed after mucosal addition of the membrane-impermeable NEM analogue, eosin-5-maleimide, was completely reversible
after washout. This suggests that the binding site for the maleimide is not accessible from the external face of the apical
membrane. Brief application of NEM at lower concentrations (1–3 min, ≤100 μm) led to partial inhibition of G
Cl
, followed by occasionally complete recovery upon washout of NEM. Recovery of voltage-activated G
Cl
was progressively attenuated and eventually disappeared after subsequent brief applications of NEM. This could reflect recruitment
of permeation/control sites from a finite pool. The data are discussed in the frame of a working model for the voltage-activated
Cl−-pathway, that contains two principle components, i.e., an anion-selective permeation path which is controlled by regulatory
protein(s).
Received: 18 December 1996/Revised: 28 April 1997 相似文献
88.
Shlomit Katz Zvy Dubinsky Chana Rothmann Zvi Malik Michael Friedlander 《Journal of phycology》1997,33(3):425-432
The novel method of Fourier transform multi-pixel spectroscopy was used for the nondestructive analysis of and comparison of pigmentation in different regions of live thalli of the red alga Porphyra linearis. Because the thallus in this alga consists of a monolayer of nonoverlapping cells, we were able to analyze the pigmentation of single cells by combining light absorbance with natural fluorescence data. From the image of each cell in the vegetative male and female reproductive and holdfast regions, more than 4 ± 104 fluorescence and absorbance spectra were obtained. Specific pigments in the different regions were localized by the use of a software program of similarity mapping followed by image construction. The reconstructed images revealed subcellular localization of each pigment according to specific spectroscopic fingerprints. The results showed that the vegetative and female reproductive cell types had a significantly higher content of phycoerythrin than of phycocyanin, and quite similar chlorophyll a levels. Most of the holdfast cells were poorly pigmented, but had more chlorophyll a than phycoerythrin or phycocyanin. The male reproductive cells contained only traces of pigments. Thus, by using Fourier transform multipixel spectroscopy, we were able to characterize the pigmentation of different regions of the thallus and follow the distribution patterns of the different pigments on the subcellular level along the differentiation gradient of the alga. 相似文献
89.
The A34R glycoprotein gene is required for induction of specialized actin-containing microvilli and efficient cell-to-cell transmission of vaccinia virus. 总被引:7,自引:5,他引:2 下载免费PDF全文
The mechanisms allowing vaccinia virus to spread from cell to cell are incompletely understood. The A34R gene of vaccinia virus encodes a glycoprotein that is localized in the outer membranes of extracellular virions. The small-plaque phenotype of an A34R deletion mutant was similar to that of mutants with deletions in other envelope genes that fail to produce extracellular vaccinia virions. Transmission electron microscopy, however, revealed that the A34R mutant produced numerous extracellular particles that were labeled with antibodies to other outer-envelope proteins and with protein A-colloidal gold. Fluorescence and scanning electron microscopy indicated that expression of the A34R protein was necessary for detection of vaccinia virus-induced actin tails, which provide motility to the intracellular enveloped form of vaccinia virus, and of virus-tipped specialized microvilli that project from the cell. The ability of vaccinia virus-infected cells to form syncytia after a brief exposure to a pH below 6, known as fusion from within, failed to occur in the absence of expression of the A34R protein; nevertheless, purified A34R- virions were capable of mediating low-pH-induced fusion from without. The present study provides genetic and microscopic evidence for the involvement of a specific viral protein in the formation or stability of actin-containing microvilli and for a role of these structures in cell-to-cell spread rather than in formation of extracellular virions. 相似文献
90.
Suresh Gunasekaran Munyaradzi Imbayagwo Louise McDonald Muthukumaran Gunasekaran Elias Manavathu 《Mycopathologia》1995,131(2):93-97
The effect of carbon sources, glucose and sucrose, and nitrogen sources such as ammonia, glutamate andl-citrulline on the activities of glutathione metabolic enzymes has been studied. Yeast and mycelial cells were used to identify changes in activity levels of glutathione reductase (GSSGR), glutathione transferase (GST), glutathione peroxidase (GPX) and -glutamyl transpeptidase (GGT). Enzyme activities from cells grown in sucrose media were lower than in glucose media regardless of the enzyme tested, morphological form, or the growth interval. In all enzymes except GST, activity was higher in yeast form than in mycelia, regardless of nitrogen source, with lower activity from 24 to 72 h than at 96 h. In citrulline media, yeast form showed the maximum GST, GGT, and GPX activity. In ammonia-amended media, mycelia showed maximum activity in GGT, whereas in glutamate media, mycelia showed the maximum activity in GST. Also, the type of nitrogen source had no effect on GPX activity in the mycelial form. Finally, changing the nitrogen source showed no significant effect on GSSGR activity, either in the yeast or mycelial form. 相似文献