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11.
Mark Andrews Alan Brown Jean-Yves Chiva David Fradet David Gordon Mark Lansdell Malcolm MacKenny 《Bioorganic & medicinal chemistry letters》2009,19(8):2329-2332
The reported selective serotonin Re-uptake Inhibitor Litoxetine was used as the starting point in the design of a range of potential SSRIs with high ease of synthetic accessibility. Preparation and subsequent optimization yielded a range of potent and highly selective SSRIs. 相似文献
12.
Relationships between the strongyloid nematodesRugopharynx delta, R. zeta, R. omega, R. longibursaris, R. mawsonae andR. sigma, all from macropodid marsupials, were investigated using allozyme data. The phylogenetic trees derived from the electrophoretic data set were congruent with those of the hosts and were consistent with the hypothesis that the species complex originated in pademelons of the genusThylogale and diversified in rock-wallabies (Petrogale spp.) and scrub wallabies of the subgenusNotamacropus. Host switching is evident only between closely related macropodid taxa. 相似文献
13.
Observed intensification of precipitation extremes, responsible for extensive societal impacts, are widely attributed to anthropogenic sources, which may include indirect effects of agricultural irrigation. However quantifying the effects of irrigation on far-downstream climate remains a challenge. We use three paired Community Earth System Model simulations to assess mechanisms of irrigation-induced precipitation trends and extremes in the conterminous US and the effect on the terrestrial carbon sink. Results suggest precipitation enhancement in the central US reduced drought conditions and increased regional carbon uptake, while further downstream, the heaviest precipitation events were more frequent and intense. Specifically, moisture advection from irrigation in the western U.S. and recycling of enhanced local convective precipitation produced very-heavy storm events that were 11% more intense and occurred 23% more frequently in the densely populated greater New York City region. 相似文献
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When ribulose bisphosphate carboxylase-oxygenase from Synechococcus (strain RRIMP N1) was precipitated under mildly acidic conditions, most of its small subunits remained in solution. The precipitated enzyme readily redissolved at neutral pH and remained as an octamer of large subunits with some small subunits still attached. Optimum pH for this separation was 5.3 and disulfide-reducing reagents were not necessary. The fraction of small subunits removed by a single precipitation increased with increasing NaCl concentration. Catalytic activity of small subunit-depleted enzyme was linearly proportional to the fraction of small subunits remaining, while the carboxylase:oxygenase activity ratio and the affinity for CO2 remained constant. When isolated small subunits were added back to depleted enzyme preparations at neutral pH, reassociation occurred with return of catalytic activity. Under the usual assay conditions at pH 7.7, the binding constant of the small subunits was estimated to be about 10(-9) M. The small subunits also bound avidly to surfaces. However, loss of small subunits from the enzyme during the course of purification was minimal. The results are consistent with a simple model in which only those large subunits which have a small subunit bound to them are catalytically competent. Thus, an essential, even if indirect, role for the small subunits in catalysis is indicated. 相似文献
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Homozygous lymphoblastoid cell lines representing various Dw subtypes of DR2 were examined for polymorphism at the DQ
locus by molecular and cellular techniques. The subtypes studied included Dw2, Dw12, and a group heterogenous by cellular typing that we shall refer to as non-Dw2/non-Dw12. Restriction fragment length polymorphism analysis of cell lines representing these subtypes revealed DQ
-specific patterns consistent with cellular typing. Two-dimensional gel electrophoresis of DQ molecules from representative cell lines revealed a structural polymorphism of DQ
among the three subtypes. The DQ
chain migrated to a position that was unique to each subtype and was consistent among various representative cell lines of each subtype. Nucleotide sequence analysis of cDNA clones of DQ
from Dw2, Dw12, and non-Dw2/non-Dw12 lines confirmed that the variability resided at the genetic level. Variability was found in the form of numerous scattered nucleotide substitutions throughout the first domain of these alleles. The DQ
gene of the non-Dw2/non-Dw12 cell line AZH was further found to be almost identical with the DQ
gene of a DR1 line (Bell et al. 1985b), implicating a common evolutionary origin of these alleles. The only difference between these two sequences was due to an apparent gene conversion event at amino acid 57. T-cell cloning experiments resulted in the derivation of Epstein-Barr virus-specific, DQw1-restricted clones that proliferated against only those cell lines that exhibited the DQ
gene common to AZH and the DR1 cell line. Thus, the polymorphism among DQ
alleles within DR2 results in subtype-specific restriction. 相似文献
18.
Blidingia minima var. ramifera is reported for the first time in eastern North America. It occurs in the Gulf of St. Lawrence, Nova Scotia and in Maine. In the estuary of the West and Rights Rivers (Antigonish Harbour, Nova Scotia) it is the most common intertidal alga and during its maximum growth period (June-August) covers 75–90% of the intertidal zone for several km of shoreline at the mouth of the Rights River. In culture, spore germination and early development were typical of the taxon as described from Europe. The taxon is raised to specific status as Blidingia ramifera stat. nov. Blidingia subsalsa is confirmed from New England based on observations of spore germination in plants from Maine and Connecticut. 相似文献
19.
This study was essentially an in vivo protection experiment designed to test further the hypothesis that stress induces release of endogenous opioids which then act at opioid receptors. Rats that were either subjected to restraint stress for 1 hr or unstressed were injected ICV with either saline or 2.5 micrograms of beta-funaltrexamine (beta-FNA), an irreversible opioid antagonist that alkylates the mu-opioid receptor. Twenty-four hours later, subjects were tested unstressed for morphine analgesia (tail-flick assay) or were sacrificed and opioid binding in brain was determined. [3H]D-Ala2NMePhe4-Gly5(ol)enkephalin (DAGO) served as a specific ligand for mu- opioid receptors, and [3H]-bremazocine as a general ligand for all opioid receptors. Rats injected with saline while stressed were significantly less sensitive to the analgesic action of morphine 24 hr later than were their unstressed counterparts. Beta-FNA pretreatment attenuated morphine analgesia in an insurmountable manner. Animals pretreated with beta-FNA while stressed were significantly more sensitive to the analgesic effect of morphine than were animals that received beta-FNA while unstressed, consistent with the hypothesis that stress induces release of endogenous opioids that would protect opioid receptors from alkylation by beta-FNA. beta-FNA caused small and similar decreases in [3H]-DAGO binding in brain of both stressed and unstressed animals. Stressed rats injected with saline tended to have increased levels of [3H]DAGO and [3H]-bremazocine binding compared to the other groups. This outcome may be relevant to the tolerance to morphine analgesia caused by stress. 相似文献
20.
We have analyzed the glycolipid markers of a recently cloned human embryonal carcinoma (EC) cell line, NTERA-2, which differentiates extensively into a variety of somatic cell types when exposed to retinoic acid. These tumor cells provide a model system that can be used to study the ontogeny of glycolipid diversity during human embryonic development. Glycolipid antigens were identified by cell surface immunofluorescence and thin-layer chromatography immunostaining using a comprehensive set of anticarbohydrate monoclonal antibodies. Undifferentiated NTERA-2 cells were found to express predominantly globo-series glycolipids, including Gb3, Gb5 (IV3GalGb4), globo-ganglioside (IV3NeuAc alpha 2----3GalGb4), globo-H (IV3Fuc alpha 1----2GalGb4), and globo-A (IV3GalNAc alpha 1----3[Fuc alpha 1----2]GalGb4). When NTERA-2 cells were induced to differentiate by culturing in the presence of 10(-5) M retinoic acid, a remarkable shift of cellular glycolipids from globo-series to lacto- and ganglio-series was observed: Globo-series structures declined, particularly during the period 7-20 days after first exposure to retinoic acid, while lacto-series structures, including fucosyl alpha 1----3 type 2 chain (Lex) and sialosyl type 2 chain, and ganglio-series structures, including GM3, GD3, 9-O-acetyl-GD3, GM2, GD2, and GT3, increased. The presence of globo-A and globo-H as the major ABH blood group antigens in undifferentiated NTERA-2 cells suggests that globo-series blood group antigens are embryonic antigens, synthesis of which switches to lacto-series during human development. Two-color immunofluorescence analysis indicated preferential expression of several ganglio- and lacto-series antigens on different subsets of differentiated cells and permitted the relationship of these subsets to the development of neurons in NTERA-2 cultures to be determined. The results suggest that glycosyltransferase, particularly those involved in controlling glycoconjugate core structure assembly, are key enzymes regulated during the differentiation of human EC cells and, by implication, during human embryogenesis. 相似文献