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101.
Dirk Schulze Markus Rapedius Tobias Krauter Thomas Baukrowitz 《The Journal of physiology》2003,552(2):357-367
Phosphatidylinositol phosphates (PIPs, e.g. PIP2 ) and long-chain acyl-CoA esters (e.g. oleoyl-CoA) are potent activators of K atp channels that are thought to link K atp channel activity to the cellular metabolism of PIPs and fatty acids. Here we show that the two types of lipid act by the same mechanism: oleoyl-CoA potently reduced the ATP sensitivity of cardiac (Kir6.2/SUR2A) and pancreatic (Kir6.2/SUR1) K atp channels in a way very similar to PIP2 . Mutations (R54Q, R176A) in the C- and N-terminus of Kir6.2 that greatly reduced the PIP2 modulation of ATP sensitivity likewise reduced the modulation by oleoyl-CoA, indicating that the two lipids interact with the same site. Polyvalent cations reduced the effect of oleoyl-CoA and PIP2 on the ATP sensitivity with similar potency suggesting that electrostatic interactions are of similar importance. However, experiments with differently charged inhibitory adenosine phosphates (ATP4- , ADP3- and 2'(3')- O -(2,4,6-trinitrophenyl)adenosine 5'-monophosphate (TNP-AMP2- )) and diadenosine tetraphosphate (Ap4 A5- ) ruled out a mechanism where oleoyl-CoA or PIP2 attenuate ATP inhibition by reducing ATP binding through electrostatic repulsion. Surprisingly, CoA (the head group of oleoyl-CoA) did not activate but inhibited K atp channels (IC50 = 265 ± 33 μM). We provide evidence that CoA and diadenosine polyphosphates (e.g. Ap4 A) are ligands of the inhibitory ATP-binding site on Kir6.2. 相似文献
102.
Haas CJ Diebold J Hirschmann A Rohrbach H Löhrs U 《Virchows Archiv : an international journal of pathology》1999,434(2):117-120
Ki-ras mutations by denaturing gradient gel electrophoresis (DGGE) and direct sequencing after microdissection. Point mutations
at codon 12 were found in 7 of 20 tumours of low malignant potential (LMP) (35%) and in 2 of 6 well-differentiated carcinomas
(33%). In contrast, no mutations were detected in the 11 poorly differentiated ovarian carcinoma samples or in the 7 serous
cystadenomas. The frequency of Ki-ras mutations in serous ovarian tumours seems to correlate with the malignant potential
of the neoplasms. The data favour the hypothesis of a de novo development of poorly differentiated ovarian carcinomas and
do not support an evolution from LMP tumours or well-differentiated carcinomas.
Received: 8 June 1998/Accepted: 8 October 1998 相似文献
103.
We have investigated the effect of histamine (HA) on spontaneous firing of dopaminergic (DA) and GABAergic neurons in the substantia nigra (SN) and the ventral tegmental area (VTA) of the rat in vitro. Single-unit extracellular recordings were obtained and drugs were bath applied. In both regions application of HA (10 and 100 μM) did not affect the firing frequency of DAergic cells, but increased the firing of GABAergic neurons. The histamine-induced excitation was blocked by the H1 receptor antagonist mepyramine (1 μM), but was unaffected by application of the H2 antagonist cimetidine (50 μM) or the H3 antagonist thioperamide (10 μM). Our results suggest that histamine does not directly inhibit dopaminergic neurons in SN and VTA, but rather that this inhibition is mediated through histamine-induced excitation of GABAergic neurons. 相似文献
104.
Is trisomy 22 in acute myeloid leukemia a primary abnormality or only a secondary change associated with inversion 16? 总被引:1,自引:0,他引:1
N Grois H Nowotny E Tyl O Krieger P Kier O A Haas 《Cancer Genetics and Cytogenetics》1989,43(1):119-129
In an attempt to confirm the existence of acute myeloid leukemia (AML) with trisomy 22, we studied three patients in whom trisomy 22 imposed as the sole karyotype abnormality. After revision of the karyotypes, however, we were able to identify an inv(16) as the important primary abnormality in all of them. Based on this experience, we investigated whether at least some of the 17 AML cases with trisomy 22 reported so far might possibly have been misinterpreted. Interestingly, ten out of 16 evaluable cases were classified as M4, some of them with bone marrow eosinophilia. As in cases with inv(16), only few metaphases contained trisomy 22. Furthermore, in at least two out of the only four published karyotypes of cases with trisomy 22, an inv(16) is evident and in the other two cases it cannot be ruled out. We therefore believe that at least some of the trisomy 22 cases mentioned in the literature are in fact only secondary changes occurring in AML with an inv(16) and suggest that future reports of AML with trisomy 22 as a specific primary abnormality can only be accepted as such if inv(16) has been excluded with appropriate methods. 相似文献
105.
Haas M. P. Geppert Holzmann Linneweh M. Allgöwer K. Hartmann R. Zenker 《Journal of molecular medicine (Berlin, Germany)》1958,36(24):1169-1172
Ohne Zusammenfassung 相似文献
106.
Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations 总被引:9,自引:1,他引:9
Meyer J; Sudbeck P; Held M; Wagner T; Schmitz ML; Bricarelli FD; Eggermont E; Friedrich U; Haas OA; Kobelt A; Leroy JG; Van Maldergem L; Michel E; Mitulla B; Pfeiffer RA; Schinzel A; Schmidt H; Scherer G 《Human molecular genetics》1997,6(1):91-98
It has previously been shown that, in the heterozygous state, mutations in
the SOX9 gene cause campomelic dysplasia (CD) and the often associated
autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one
recurrent mutation were characterized in one SOX9 allele each, and in one
case, no mutation was found. Four missense mutations are all located within
the high mobility group (HMG) domain. They either reduce or abolish the
DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense
and three frameshift mutations identified, two leave the C-terminal
transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or
almost completely intact. When tested in cell transfection experiments, the
recurrent nonsense mutation Y440X, found in two patients who survived for
four and more than 9 years, respectively, exhibits some residual
transactivation ability. In contrast, a frameshift mutation extending the
protein by 70 residues at codon 507, found in a patient who died shortly
after birth, showed no transactivation. This is apparently due to
instability of the mutant SOX9 protein as demonstrated by Western blotting.
Amino acid substitutions and nonsense mutations are found in patients with
and without XY sex reversal, indicating that sex reversal in CD is subject
to variable penetrance. Finally, none of 18 female patients with XY gonadal
dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP
assays, providing evidence that SOX9 mutations do not usually result in XY
sex reversal without skeletal malformations.
相似文献
107.
108.
Characterization of FcepsilonRI-bearing CD123 blood dendritic cell antigen-2 plasmacytoid dendritic cells in atopic dermatitis 总被引:3,自引:0,他引:3
Novak N Allam JP Hagemann T Jenneck C Laffer S Valenta R Kochan J Bieber T 《The Journal of allergy and clinical immunology》2004,114(2):364-370
BACKGROUND: The high-affinity receptor for IgE (FcepsilonRI) on myeloid dendritic cells has been shown to play a major role in atopic dermatitis (AD). Plasmacytoid dendritic cells (pDCs), which are instrumental in the defense of viral infections, are present in reduced amounts in the skin of patients with AD, which is characterized by a high susceptibility to viral infections. OBJECTIVE: We explored phenotypical and functional characteristics of pDC in the peripheral blood of patients with AD and healthy individuals. METHODS: Blood dendritic cell antigen-2+CD123+ pDCs were enriched from the peripheral blood of patients with AD and studied in functional assays. RESULTS: Skin-homing molecules such as cutaneous lymphocyte antigen and L-selectin CD62L were expressed in lower levels on pDCs of patients with AD. pDCs expressed high amounts of IgE-occupied FcepsilonRI. Further, FcepsilonRI aggregation on pDCs impaired the surface expression of MHC I and II, induced the production of IL-10, and enhanced the apoptosis of pDCs. Importantly, FcepsilonRI preactivated pDC produced less IFN-alpha and IFN-beta after stimulation with CpG motifs and enhanced the outcome of immune responses of the TH2 type. CONCLUSION: From these data, we conclude that FcepsilonRI-bearing pDCs from patients with AD (1) are different from pDCs of healthy individuals, (2) might be important in the pathophysiology of AD, and (3) contribute to the enhanced susceptibility of patients with AD to viral infections. 相似文献
109.
110.