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161.
Herr DR Fyrst H Phan V Heinecke K Georges R Harris GL Saba JD 《Development (Cambridge, England)》2003,130(11):2443-2453
Sphingosine-1-phosphate is a sphingolipid metabolite that regulates cell proliferation, migration and apoptosis through specific signaling pathways. Sphingosine-1-phosphate lyase catalyzes the conversion of sphingosine-1-phosphate to ethanolamine phosphate and a fatty aldehyde. We report the cloning of the Drosophila sphingosine-1-phosphate lyase gene (Sply) and demonstrate its importance for adult muscle development and integrity, reproduction and larval viability. Sply expression is temporally regulated, with onset of expression during mid-embryogenesis. Sply null mutants accumulate both phosphorylated and unphosphorylated sphingoid bases and exhibit semi-lethality, increased apoptosis in developing embryos, diminished egg-laying, and gross pattern abnormalities in dorsal longitudinal flight muscles. These defects are corrected by restoring Sply expression or by introduction of a suppressor mutation that diminishes sphingolipid synthesis and accumulation of sphingolipid intermediates. This is the first demonstration of novel and complex developmental pathologies directly linked to a disruption of sphingolipid catabolism in metazoans. 相似文献
162.
Tucker G 《Current opinion in biotechnology》2003,14(2):221-225
Plants can provide most of the nutrients required in the human diet; however, the major staple crops are often deficient in some of these nutrients. Thus, malnutrition, with respect to micronutrients like vitamin A, iron and zinc, affects >40% of the world's population. Advances in molecular biology are being exploited to produce crops enhanced in these key nutrients. Other nutritional targets include the modification of fatty acid composition and the enhancement of antioxidant levels, particularly carotenoids, such as lycopene, and flavonoids. However, the benefit of these 'biofortified' crops to human nutrition remains to be elucidated. 相似文献
163.
Tucci FC Zhu YF Guo Z Gross TD Connors PJ Struthers RS Reinhart GJ Saunders J Chen C 《Bioorganic & medicinal chemistry letters》2003,13(19):3317-3322
A new class of small molecule GnRH antagonists, the 1-arylmethyl-3-(1-methyl-2-amino)ethyl-5-aryl-6-methyluracils, was designed and a novel stereoselective synthesis for these compounds was developed. The stereochemical integrities of key intermediates (S)-6 and (R)-6 were confirmed by a combination of X-ray crystallography and chiral HPLC determinations. SAR studies were performed, which allowed the identification of derivatives (R)-9f, (R)-9h and (R)-12 as potent hGnRH antagonists (K(i)=20 nM). 相似文献
164.
Role of JNK in hypertonic activation of Cl--dependent Na+/H+ exchange in Xenopus oocytes 总被引:1,自引:0,他引:1
Goss Greg G.; Jiang Lianwei; Vandorpe David H.; Kieller Dawn; Chernova Marina N.; Robertson Marilyn; Alper Seth L. 《American journal of physiology. Cell physiology》2001,281(6):C1978
In the course of studying the hypertonicity-activated iontransporters in Xenopus oocytes, we found that activation ofendogenous oocyte Na+/H+ exchange activity(xoNHE) by hypertonic shrinkage required Cl, with anEC50 for bath [Cl] of ~3 mM. Thisrequirement for chloride was not supported by several nonhalide anionsand was not shared by xoNHE activated by acid loading.Hypertonicity-activated xoNHE exhibited an unusual rank order ofinhibitory potency among amiloride derivatives and was blocked byCl transport inhibitors. Chelation of intracellularCa2+ by injection of EGTA blocked hypertonic activation ofxoNHE, although many inhibitors of Ca2+-related signalingpathways were without inhibitory effect. Hypertonicity activated oocyteextracellular signal-regulated kinase 1/2 (ERK1/2), but inhibitors ofneither ERK1/2 nor p38 prevented hypertonic activation of xoNHE.However, hypertonicity also stimulated a Cl-dependentincrease in c-Jun NH2-terminal kinase (JNK) activity. Inhibition of JNK activity prevented hypertonic activation of xoNHE butnot activation by acid loading. We conclude that hypertonic activationof Na+/H+ exchange in Xenopusoocytes requires Cl and is mediated by activation of JNK. 相似文献
165.
Brereton Helen M. Harland M. Lyn Auld Amanda M. Barritt Greg J. 《Molecular and cellular biochemistry》2000,214(1):63-74
The role of the TRP-1 protein, an animal cell homologue of the Drosophila transient receptor potential Ca2+ channel, in store-operated Ca2+ inflow in Xenopus laevis oocytes was investigated. A strategy involving RT-PCR and 3 and 5 rapid amplification of cDNA ends (RACE) was used to confirm and extend previous knowledge of the nucleotide and predicted amino acid sequences of Xenopus TRP-1 (xTRP-1). The predicted amino acid sequence was used to prepare an anti-TRP-1 polyclonal antibody which detected the endogenous oocyte xTRP-1 protein and the human TRPC-1 protein expressed in Xenopus oocytes. Ca2+ inflow (measured using fura-2) initiated by 3-deoxy-3-fluoroinositol 1,4,5-trisphosphate (InsP3F) or lysophosphatidic acid (LPA) was completely inhibited by low concentrations of lanthanides (IC50 = 0.5 M), indicating that InsP3F and LPA principally activate store-operated Ca2+ channels (SOCs). Antisense cRNA or antisense oligodeoxynucleotides, based on different regions of the xTRP-1 cDNA sequence, when injected into Xenopus oocytes, did not inhibit InsP3F-, LPA- or thapsigargin-stimulated Ca2+ inflow. Oocytes expressing the hTRPC-1 protein, which is 96% similar to xTRP-1, exhibited no detectable enhancement of either basal or InsP3F-stimulated Ca2+ inflow and only a very small enhancement of LPA-stimulated Ca2+ inflow compared with control oocytes. It is concluded that the endogenous xTRP-1 protein is unlikely to be responsible for Ca2+ inflow through the previously-characterised Ca2+-specific SOCs which are found in Xenopus oocytes. It is considered that xTRP-1 is likely to be a receptor-activated non-selective cation channel such as the channel activated by maitotoxin. 相似文献
166.
Gravity independence of seed-to-seed cycling in Brassica rapa 总被引:2,自引:0,他引:2
Musgrave ME Kuang A Xiao Y Stout SC Bingham GE Briarty LG Levenskikh MA Sychev VN Podolski IG 《Planta》2000,210(3):400-406
Growth of higher plants in the microgravity environment of orbital platforms has been problematic. Plants typically developed
more slowly in space and often failed at the reproductive phase. Short-duration experiments on the Space Shuttle showed that
early stages in the reproductive process could occur normally in microgravity, so we sought a long-duration opportunity to
test gravity's role throughout the complete life cycle. During a 122-d opportunity on the Mir space station, full life cycles
were completed in microgravity with Brassica rapa L. in a series of three experiments in the Svet greenhouse. Plant material was preserved in space by chemical fixation, freezing,
and drying, and then compared to material preserved in the same way during a high-fidelity ground control. At sampling times
13 d after planting, plants on Mir were the same size and had the same number of flower buds as ground control plants. Following
hand-pollination of the flowers by the astronaut, siliques formed. In microgravity, siliques ripened basipetally and contained
smaller seeds with less than 20% of the cotyledon cells found in the seeds harvested from the ground control. Cytochemical
localization of storage reserves in the mature embryos showed that starch was retained in the spaceflight material, whereas
protein and lipid were the primary storage reserves in the ground control seeds. While these successful seed-to-seed cycles
show that gravity is not absolutely required for any step in the plant life cycle, seed quality in Brassica is compromised by development in microgravity.
Received: 3 August 1999 / Accepted: 27 August 1999 相似文献
167.
Runke G Maier E O'Neil JD Benz R Court DA 《Journal of bioenergetics and biomembranes》2000,32(6):563-570
Mitochondrial porin facilitates the diffusion of small hydrophilic molecules across the mitochondrial outer membrane. Despite low sequence similarity among porins from different species, a glycine-leucine-lysine (GLK) motif is conserved in mitochondrial and Neisseria porins. To investigate the possible roles of these conserved residues, including their hypothesized participation in ATP binding by the protein, we replaced the lysine residue of the GLK motif of Neurospora crassa porin with glutamic acid through site-directed mutagenesis of the corresponding gene. Although the pores formed by this protein have size and gating characteristics similar to those of the wild-type protein, the channels formed by GLEporin are less anion selective than the wild-type pores. The GLEporin retains the ability to be cross linked to [-32P]ATP, indicating that the GLK sequence is not essential for ATP binding. Furthermore, the pores formed by both GLEporin and the wild-type protein become more cation selective in the presence of ATP. Taken together, these results support structural models that place the GLK motif in a part of the ion-selective -barrel that is not directly involved in ATP binding. 相似文献
168.
Spinach (Spinacea oleracea L.) nitrate reductase (NR) is inactivated by phosphorylation on serine-543, followed by binding of the phosphorylated enzyme
to 14-3-3 proteins. We purified one of several chromatographically distinct NRserine-543 kinases from spinach leaf extracts, and established by Edman sequencing of 80 amino acid residues that it is a calcium-dependent
(calmodulin-domain) protein kinase (CDPK), with peptide sequences very similar to Arabidopsis CDPK6 (accession no. U20623; also known as CPK3). The spinach CDPK was recognized by antibodies raised against Arabidopsis CDPK. Nitrate reductase was phosphorylated at serine-543 by bacterially expressed His-tagged CDPK6, and the phosphorylated
NR was inhibited by 14-3-3 proteins. However, the bacterially expressed CDPK6 had a specific activity approx. 200-fold lower
than that of the purified spinach enzyme. The physiological control of NR by CDPK is discussed, and the regulatory properties
of the purified CDPK are considered with reference to current models for reversible intramolecular binding of the calmodulin-like
domain to the autoinhibitory junction of CDPKs.
Received: 12 February 1998 / Accepted: 28 May 1998 相似文献
169.
Mitochondrial Inheritance Is Delayed in Saccharomyces cerevisiae Cells Lacking the Serine/Threonine Phosphatase PTC1 总被引:2,自引:0,他引:2
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Amy D. Roeder Greg J. Hermann Brian R. Keegan Stephanie A. Thatcher Janet M. Shaw 《Molecular biology of the cell》1998,9(4):917-930
In wild-type yeast mitochondrial inheritance occurs early in the cell cycle concomitant with bud emergence. Cells lacking the PTC1 gene initially produce buds without a mitochondrial compartment; however, these buds later receive part of the mitochondrial network from the mother cell. Thus, the loss of PTC1 causes a delay, but not a complete block, in mitochondrial transport. PTC1 encodes a serine/threonine phosphatase in the high-osmolarity glycerol response (HOG) pathway. The mitochondrial inheritance delay in the ptc1 mutant is not attributable to changes in intracellular glycerol concentrations or defects in the organization of the actin cytoskeleton. Moreover, epistasis experiments with ptc1Δ and mutations in HOG pathway kinases reveal that PTC1 is not acting through the HOG pathway to control the timing of mitochondrial inheritance. Instead, PTC1 may be acting either directly or through a different signaling pathway to affect the mitochondrial transport machinery in the cell. These studies indicate that the timing of mitochondrial transport in wild-type cells is genetically controlled and provide new evidence that mitochondrial inheritance does not depend on a physical link between the mitochondrial network and the incipient bud site. 相似文献
170.
Stapanian Martin A. Sundberg Scott D. Baumgardner Greg A. Liston Aaron 《Plant Ecology》1998,139(1):49-62
A probability-based sampling scheme was used to survey plant species composition in forests of 16 states in seven geopolitical regions of the United States (California, Colorado, Minnesota, and parts of the Pacific Northwest, Southeast, Mid-Atlantic, and Northeast) in 1994. The proportion of alien species relative to the total species number and to canopy cover in the ground stratum (0–0.6 m height) was evaluated in 279 plots. Visually evident anthropogenic disturbances (e.g., artificial regeneration, logging, prescribed burning, and grazing by livestock), if any, were recorded on each plot. In each of the seven regions we quantified (1) the percentage of the number of species and total cover comprised of alien species, (2) the difference in these percentages for disturbed and undisturbed plots, and (3) the origin or native range for the alien species.The percentage of alien species ranged from approximately 4.5% (Colorado) to approximately 13.2% (California). The percentage of alien species cover ranged from approximately 1.5% in Colorado to 25% in California. In five regions, species introduced from temperate Eurasia comprised the largest proportion of alien species and cover. In the Southeast, species introduced from far eastern and subtropical Asia dominated the alien flora. In the Mid-Atlantic, the majority of alien species was Eurasian and the majority of alien species cover consisted of far eastern and subtropical Asian species.The proportion of plots in which at least one alien species was recorded was significantly higher in disturbed than undisturbed plots in the Southeast and marginally significantly higher ($p=0.053$) in the Northeast. These results are consistent with other published studies that indicate that anthropogenic disturbance affects the structure and composition of both the ground stratum and upper canopy of forest habitats. In other regions, however, no significant differences were found. 相似文献