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21.
C A Brown K Neote A Leung R A Gravel D J Mahuran 《The Journal of biological chemistry》1989,264(36):21705-21710
Lysosomal beta-hexosaminidase (beta-N-acetylhexosaminidase, EC 3.2.1.52) occurs in two major isozyme forms, hexosaminidase A (alpha beta) and hexosaminidase B (beta beta). Although dimer formation is required for enzymatic activity, both subunits contain active sites which share many common substrates. However, the alpha subunit alone confers on hexosaminidase A the specificity for negatively charged substrates, e.g. GM2 ganglioside. Recently, a point mutation, producing a single amino acid substitution in the alpha subunit (Arg178-His), has been found to be associated with the B1 variant phenotype of Tay-Sachs disease (Ohno, K., and Suzuki, K. (1988) J. Neurochem. 50, 316-318). This variant is characterized by normal levels of hexosaminidase A as measured by a common artificial substrate, but an absence of activity toward alpha subunit-specific substrates. However, because of the presence of an active beta subunit in the mutant hexosaminidase A, it has not been possible to determine whether the affected alpha subunit has undergone a change in substrate specificity or become totally inactive. In order to define the full effect of the B1 mutation we have taken advantage of the common evolutionary origin of the genes coding for the alpha and beta subunits. Since the B1 mutation occurs in a region of extended identity between the two subunits, we have duplicated the Arg178-His mutation in a cDNA coding for the human beta subunit (Arg211-His). By expression of the mutant construct in monkey COS cells we have been able to examine the effect of this mutation on beta subunits which are capable of forming stable, active homodimers, an experiment that could not readily be accomplished with heterodimeric hexosaminidase A. Our data show that beta homodimers containing the Arg211-His substitution are formed and are transported into the lysosome in a manner identical to that of normal pro-hexosaminidase B. However, the mutant homodimers are processed at a slower rate and are less stable in the lysozyme. Their most striking feature was a total lack of normal hexosaminidase B activity. We conclude that while the effect of the Arg178-His substitution is not strictly limited to the active site, the severe B1 phenotype results from a totally inactive alpha-subunit in hexosaminidase A. 相似文献
22.
Transforming growth factor-alpha in the mammalian brain. Immunohistochemical detection in neurons and characterization of its mRNA 总被引:5,自引:0,他引:5
J E Kudlow A W Leung M S Kobrin A J Paterson S L Asa 《The Journal of biological chemistry》1989,264(7):3880-3883
In this communication, we demonstrate that adult mammalian brain neurons express transforming growth factor-alpha (TGF-alpha). We used the anti-TGF-alpha monoclonal antibody, MF9, to immunohistochemically localize TGF-alpha in human and rat brain. We found specific immunoreactivity in neurons throughout the brain which was not a result of cross-reactivity of MF9 with the neuropeptide, synenkephalin. Northern blot analysis of bovine and rat brain RNA using human and rat TGF-alpha cDNA probes, respectively, revealed a single 4.8-kilobase pair mRNA with approximately equal abundance in the bovine brainstem, cerebellum, hypothalamus, and cerebral cortex. Fetal rat brain had about 2-fold more TGF-alpha mRNA than did adult rat. The brain TGF-alpha cDNA was cloned from a human neonatal brainstem library. Four identical clones were isolated after screening 10(6) recombinant lambda gt11 phage. The sequence of the 894-base pair cDNA was virtually identical with the cDNA isolated from a human renal cell carcinoma. A single alanine codon was deleted in the brain cDNA at an exon-exon junction. The alanine deletion is within the amino-terminal region of the TGF-alpha precursor that is thought to be removed by proteolytic processing of the precursor to the mature growth factor. These studies indicate that the normal mammalian brain neurons express TGF-alpha. 相似文献
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26.
Differential regulation of vascular cell adhesion molecule 1 gene expression by specific NF-kappa B subunits in endothelial and epithelial cells. 总被引:21,自引:5,他引:16 下载免费PDF全文
H B Shu A B Agranoff E G Nabel K Leung C S Duckett A S Neish T Collins G J Nabel 《Molecular and cellular biology》1993,13(10):6283-6289
27.
D. O. Carpenter G. Kemenes K. Elekes M. Leung G. Stefano K. S.-Rózsa J. Salánki 《Cellular and molecular neurobiology》1995,15(2):239-256
Summary 1. We have used biochemical, immunocytochemical, and electrophysiological techniques to evaluate the role of opioid peptides in the central nervous system of the marine mollusc,Aplysia california.2. Binding studies using3H-d-Ala2, met-enkephalinamide (3H-DAMA) showed a single class of high-affinity binding sites with aK
d of 1.3 nM and a binding density of 45 pmol/g.3. HPLC extracts of ganglia revealed multiple peaks with immunoreactivity for either leu (LEU-IR)- or met-enkephalin (MET-IR), but the amounts were not uniformly distributed in all ganglia.4. LEU-IR and MET-IR neurons were demonstrated immunocytochemically in all ganglia, but MET-IR neurons were more frequent and were concentrated in pedal and pleural ganglia. While absorption control studies abolished MET-IR, LEU-IR was only partially abolished in the neuropil.5. In electrophysiological studies, both depolarizing and hyperpolarizing responses were found tod-Ala2-leu-enkephalin (DALEU) andd-Ala2-met enkephalin (DAMET) on some and different neurons.6. HPLC fractions from regions with retention times corresponding to authentic leu- or met-enkephalin showed physiologic responses similar to those of DALEU and DAMET, respectively.7. These studies suggest that a variety of endogeneous opioid peptides play physiologically important roles in the nervous system ofAplysia, including but not necessarily limited to leu- and met-enkephalin. 相似文献
28.
The population dynamics of Metapenaeus ensis in a traditional tidal shrimp pond (locally known as gei wai ) at the Mai Po Marshes Nature Reserve, Hang Kong, were studied over a 29-month period. The population of M. ensis was dominated by either one or two age groups throughout the year. Life span was < 16 months. M. ensis is sexually dimorphic in terms of size, with females growing faster and attaining a larger maximum size than males. The sex ratio did not differ significantly from 1:1. The prawns do not mature and reproduce in the gei wai so that the population is sustained by postlarval immigration which begins in June and ends in December, with peaks in August and November. The gei wai population of M. ensis is characterized by slower growth, lower maximum attainable size, shorter life span, reproductive sterility and an incomplete life cycle, as compared with 'natural' population in the coastal waters of Hong Kong. 相似文献
29.
Qu Zhengxing; Sharkey Robert M.; Hansen Hans J.; Goldenberg David M.; Leung Shui-on 《Glycobiology》1997,7(6):803-809
Two humanized antibody mutants, hLL2HCN1 and hLL2HCN5, engineeredwith CH1 domain-appended carbohydrates (CHOs) were generatedto facilitate site-specific conjugation of radionudides andanti-cancer drugs to antibodies. Such site-specific conjugationmay minimize the incidence of immunoreactlvity perturbationas is often observed with random conjugation. Since the compositionsand structures of CHOs are important in determining the chemistry,efficiency, and extent of conjugation, the sequences of theCH1-appended CHOs were determined by exoglycosidase digestionsand fluorophore-assisted CHO electrophoresis (FACE). The CHOspecies attached at HCN1 and HCN5 sites in hLL2HCN1 and IJLL2HCN5,respectively, were distinct from each other, heterogeneous,and extensively processed. All of these CHOs were corefucosylatedcomplex-type oligosaccharides and contained Gal (galactose)and GlcNAc (N-acetylglucosamine) residues in the outer branches.Some of the outer branches were composed of Gal 相似文献
30.
H.C. Chan S.H. Law P.S. Leung L.X.M. Fu P.Y.D. Wong 《The Journal of membrane biology》1997,156(3):241-249
The β-adrenergic (cAMP-dependent) regulation of Cl− conductance is defective in cystic fibrosis (CF). The present study explored alternative regulation of anion secretion in
CF pancreatic ductal cells (CFPAC-1) by angiotensin II (AII) using the short-circuit current (I
SC
) technique. An increase in I
SC
could be induced in CFPAC-1 cells by basolateral or apical application of AII in a concentration-dependent manner (EC50 at 3 μm and 100 nm, respectively). Angiotensin receptor subtypes were identified using specific antagonists, losartan and PD123177, for AT1 and AT2 receptors, respectively. It was found that losartan (1 μm) could completely inhibit the AII-induced I
SC
, whereas, PD123177 exerted insignificant effect on the I
SC
, indicating predominant involvement of AT1 receptors. The presence of AT1 receptors in CFPAC-1 cells was also demonstrated by immunohistochemical studies using specific antibodies against AT1 receptors. Confocal microscopic study demonstrated a rise in intracellular Ca2+ upon stimulation by AII indicating a role of intracellular Ca2+ in mediating the AII response. Depletion of intracellular but not extracellular pool of Ca2+ diminished the AII-induced I
SC
. Treatment of the monolayers with a Cl− channel blocker, DIDS, markedly reduced the I
SC
, indicating that a large portion of the AII-activated I
SC
was Cl−-dependent. AII-induced I
SC
was also observed in monolayers whose basolateral membranes had been permeabilized by nystatin, suggesting that the I
SC
was mediated by apical Cl− channels. Our study indicates an AT1-mediated Ca2+-dependent regulatory mechanism for anion secretion in CF pancreatic duct cells which may be important for the physiology
and pathophysiology of the pancreas.
Received: 17 June 1996/Revised: 14 November 1996 相似文献