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71.
Boxall S Stanton T Hirai K Ward V Yasui T Tahara H Tamori A Nishiguchi S Shiomi S Ishiko O Inaba M Nishizawa Y Dawes R Bodmer W Beverley PC Tchilian EZ 《Human molecular genetics》2004,13(20):2377-2384
The CD45 antigen is a haemopoietic cell specific tyrosine phosphatase essential for antigen receptor mediated signalling in lymphocytes. Expression of different patterns of alternatively spliced CD45 isoforms is associated with distinct functions. We recently identified a polymorphism in exon 6 (A138G) of the gene encoding CD45 (PTPRC) that results in altered CD45 splicing. The 138G allele is present at a high frequency among Japanese (23.7%), with 5.1% individuals homozygous for the G allele. In this study we show that the A138G polymorphism is the cause of altered CD45 isoform expression, promoting splicing towards low molecular weight CD45 isoforms. We further report that the frequency of A138G heterozygotes is significantly reduced in number in cohorts of patients with autoimmune Graves' disease or hepatitis B infection, whereas G138G homozygotes are absent from a cohort of Hashimoto's thyroiditis patients. We also show that 138G individuals exhibit altered cytokine production in vitro and an increased proportion of memory T cells. These data suggest that the 138G variant allele strongly influences these diseases by modulation of immune mechanisms and may have achieved its high frequency as a result of a natural selection probably related to pathogen resistance. 相似文献
72.
Over the past 100 years Drosophila has been developed into an outstanding model system for the study of evolutionary processes. A fascinating aspect of evolution
is the differentiation of sex chromosomes. Organisms with highly differentiated sex chromosomes, such as the mammalian X and
Y, must compensate for the imbalance in gene dosage that this creates. The need to adjust the expression of sex-linked genes
is a potent force driving the rise of regulatory mechanisms that act on an entire chromosome. This review will contrast the
process of dosage compensation in Drosophila with the divergent strategies adopted by other model organisms. While the machinery of sex chromosome compensation is different
in each instance, all share the ability to direct chromatin modifications to an entire chromosome. This review will also explore
the idea that chromosome-targeting systems are sometimes adapted for other purposes. This appears the likely source of a chromosome-wide
targeting system displayed by the Drosophila fourth chromosome. 相似文献
73.
Busse A Sánchez MA Monterroso V Alvarado MV León P 《American journal of medical genetics. Part A》2004,(2):190-194
Four affected siblings in a Costa Rican family presented an aggressive polyneuropathy with widespread involvement of many visceral organs and onset during the third decade of life with rapid loss of muscle mass in the lower limbs and severe dysautonomy. The medical histories include vitreous opacity, cardiac enlargement, dermal and gastrointestinal infiltration, and autonomic dysfunction including circulatory compromise and gastrointestinal disturbances. Histological studies using Congo red stain and immunohistochemical assays with antibodies against the transthyretin (TTR) protein showed widespread deposition of amyloid in extracellular areas, including dermis and gastrointestinal lamina propia, endo- and perineural spaces, and vascular walls. A mutation search in the transthyretin (ttr) gene was performed seeking the cause of this severe form of familial amyloidotic polyneuropathy (FAP). We applied single-stranded conformational polymorphism (SSCP)-analyses followed by sequencing of the four exons of the ttr gene, revealing a point mutation in exon 3, a G to A transition that causes a Glu54Lys codon change. Western blots of plasma proteins incubated with anti-transthyretin antibodies after gel electrophoresis provided separation of wild-type and mutant TTR protein in affected family members. 相似文献
74.
75.
Robinson VL Hickson JA Vander Griend DJ Dubauskas Z Rinker-Schaeffer CW 《Clinical & experimental metastasis》2003,20(1):25-30
MAP kinase kinase 4 (MKK4) is a member of the stress-activated protein kinase (SAPK) signaling cascade and is involved in the regulation of many cellular processes. We have recently demonstrated a functional role for MKK4 in the suppression of metastases. In this review, we discuss the established cellular and biochemical functions of MKK4, as well as a new function for MKK4 as a metastasis suppressor gene. Because of the importance of signaling studies to this translational work, a detailed example of the strategy and tools that can be employed to define the biochemical mechanism of MKK4-mediated metastasis suppression is presented. Finally, the potential therapeutic utility of these findings is discussed. 相似文献
76.
Event-related potentials (ERPs) from 134 children were obtained at 3 and 8 years of age and recorded to a series of consonant-vowel speech syllables and their nonspeech analogues. The HOME inventory was administered to these same children at 3 and 8 years of age and the sample was divided into 2 groups (low vs. high) based on their HOME scores. Discriminant functions analyses using ERP responses to speech and non-speech analogues successfully classified HOME scores obtained at 3 and 8 years of age and discriminated between children who received low vs. high levels of stimulation for language and reading. 相似文献
77.
The roles of individual eukaryotic translation initiation factors in ribosomal scanning and initiation codon selection 总被引:13,自引:0,他引:13
To elucidate an outline of the mechanism of eukaryotic translation initiation, 48S complex formation was analyzed on defined mRNAs in reactions reconstituted in vitro from fully purified translation components. We found that a ribosomal 40S subunit, eukaryotic initiation factor (eIF) 3, and the eIF2 ternary complex form a 43S complex that can bind to the 5'-end of an unstructured 5'-untranslated region (5'-UTR) and in the presence of eIF1 scan along it and locate the initiation codon without a requirement for adenosine triphosphate (ATP) or factors (eIF4A, eIF4B, eIF4F) associated with ATP hydrolysis. Scanning on unstructured 5'-UTRs was enhanced by ATP, eIFs 4A and 4B, and the central domain of the eIF4G subunit of eIF4F. Their omission increased the dependence of scanning on eIFs 1 and 1A. Ribosomal movement on 5'-UTRs containing even weak secondary structures required ATP and RNA helicases. eIF4F was essential for scanning, and eIFs 4A and 4B were insufficient to promote this process in the absence of eIF4F. We report that in addition to its function in scanning, eIF1 also plays a principal role in initiation codon selection. In the absence of eIF1, 43S complexes could no longer discriminate between cognate and noncognate initiation codons or sense the nucleotide context of initiation codons and were able to assemble 48S complexes on 5'-proximal AUG triplets located only 1, 2, and 4 nt from the 5'-end of mRNA. 相似文献
78.
Irina V. Tereschenko Victoria M. Basham Bruce A.J. Ponder Paul D.P. Pharoah 《Human mutation》2002,19(2):184-184
We have screened index cases from 25 Russian breast/ovarian cancer families for germ‐line mutations in all coding exons of the BRCA1 and BRCA2 genes, using multiplex heteroduplex analysis. In addition we tested 22 patients with breast cancer diagnosed before age 40 without family history and 6 patients with bilateral breast cancer. The frequency of families with germline mutations in BRCA was 16% (4/25). One BRCA1 mutation, 5382insC, was found in three families. The results of present study, and those of a separate study of 19 breast‐ovarian cancer families, suggest that BRCA1 5382insC is a founder mutation in the Russian population. Three BRCA2 mutations were found in patients with breast cancer without family history: two in young patients and one in patients with bilateral breast cancer. Four novel BRCA2 mutations were identified: three frameshift (695insT, 1528del4, 9318del4) and one nonsense (S1099X). © 2002 Wiley‐Liss, Inc. 相似文献
79.
The American College of Sports Medicine (ACSM) recommends that, as a general rule for health purposes, individuals should
exercise at 40%–85% of their maximal oxygen uptakes. Moreover, it has been suggested that 55%–90% of the maximal heart rate
may be used as an alternative estimate of these percentage maximal oxygen uptake values. The present study examined the relationship
between percentage peak heart rate (% HRpeak) and percentage peak oxygen uptake (%
) during steady-state incremental intensity wheelchair propulsion of 16 élite, male wheelchair racers (WR). Oxygen uptake
was determined during each submaximal exercise stage and heart rate (HR) was continuously monitored. The
was subsequently determined using a separate protocol. Linear regression equations of % HRpeak versus %
for each participant included % HRpeak values corresponding to 40%, 60%, 80% and 85%
. The linear regression equation, derived as the group mean of the slope and intercept terms determined for each individual,
was:
. The group mean of the individual correlation coefficients for the
relationship was 0.99. The values of % HRpeak for each of the %
values below 85% were significantly greater (P<0.01) than those suggested by the ACSM. This suggests that the ACSM guidelines below 85%
, based on % HRpeak, may underestimate the relative exercise intensity (i.e. %
) in the WR population. However, in élite level WR, % HRpeak can be recommended as an alternative estimate of %
at wheelchair propulsion intensities of 85%
or more.
Electronic Publication 相似文献
80.