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121.
Cees DM Ruijs Bregje D Onwuteaka-Philipsen Gerrit van der Wal Ad JFM Kerkhof 《BMC palliative care》2009,8(1):16-10
Background
Unbearable suffering is an important issue in end-of-life decisions. However, there has been no systematic, prospective, patient-oriented research which has focused on unbearable suffering, nor is there a suitable measurement instrument. This article describes the methodological development of a quantitative instrument to measure the nature and intensity of unbearable suffering, practical aspects of its use in end-stage cancer patients in general practice, and studies content validity and psychometric properties. 相似文献122.
Summary
Policy decisions about the allocation of current and future resources should be based on the most accurate predictions possible. A functional data analysis (FDA) approach improves the understanding of current trends and future incidence of injuries. FDA provides more valid and reliable long-term predictions than commonly used methods. 相似文献123.
A. Finch M. Wang A. Fine L. Atri S. Khalouei M. Pupavac B. Rosen A. Eisen C. Elser G. Charames K. Metcalfe M.C. Chang S.A. Narod J. Lerner‐Ellis 《Clinical genetics》2016,89(3):304-311
In 2001, genetic testing for BRCA1 and BRCA2 was introduced in Ontario, for women at high‐risk of breast or ovarian cancer. To date over 30,000 individuals have been tested throughout Ontario. Testing was offered to all Ontario residents who were eligible under any of 13 criteria. We report the results of tests conducted at Mount Sinai Hospital from 2007 to 2014. A total of 4726 individuals were tested, 764 (16.2%) were found to carry a pathogenic variant (mutation). Among 3684 women and men who underwent testing without a known familial BRCA mutation, 331 (9.0%) were found to carry a mutation. Among 1042 women and men tested for a known family mutation, 433 (41.6%) were positive. There were 603 female mutation carriers, of these, 303 were affected with breast or ovarian cancer (50%) and 16 with another cancer (2.3%). Of 284 unaffected female carriers, 242 (85%) were tested for a known family mutation and 42 (15%) were the first person in the family to be tested. By placing greater emphasis on recruiting unaffected female relatives of known mutation carriers for testing, greater than one‐half of newly identified carriers will be unaffected. 相似文献
124.
Guidelines are an important means by which professional associations and governments have sought to improve the quality and cost-effectiveness of disease management for infectious diseases. Prescribing of initial antibiotic therapy for community-acquired respiratory tract infections (RTIs) is primarily empiric and physicians may often have a limited appreciation of bacterial resistance. Recent guidelines for managing RTIs have adopted a more evidence-based approach. This process has highlighted important gaps in the existing knowledge base, e.g. concerning the impact of resistance on the effectiveness of oral antibiotics for outpatient community-acquired pneumonia and the level of resistance that should prompt a change in empiric prescribing. In upper RTIs, the challenge is to identify patients in whom antibiotic therapy is warranted. Concentrated, sustained efforts are needed to secure physicians' use of guidelines. The information should be distilled into a simple format available at the point of prescribing and supported by other behavioral change techniques (e.g. educational outreach visits). Advances in information technology offer the promise of more dynamic, computer-assisted forms of guidance. Thus, RTI prescribing guidelines and other prescribing support systems should help control bacterial resistance in the community. However, their effect on resistance patterns is largely unknown and there is an urgent need for collaborative research in this area. Rapid, cost-effective diagnostic techniques are also required and new antibiotics will continue to have a role in disease management. 相似文献
125.
Genotype-phenotype correlation for nucleotide substitutions in the IgII- IgIII linker of FGFR2 总被引:3,自引:3,他引:3
126.
Sequences from higher primates orthologous to the human Xp/Yp telomere junction region reveal gross rearrangements and high levels of divergence 总被引:2,自引:2,他引:2
A high level of sequence polymorphism combined with linkage disequilibrium
has created a limited number of highly diverged haplotypes across the human
Xp/Yp telomere junction region. To gain insight into the unusual genetic
characteristics of this region, we have examined the orthologous sequences
in the common chimpanzee (Pan troglodytes ), the gorilla (Gorilla gorilla)
and the orang-utan (Pongo pygmaeus). Divergence from the human Xp/Yp
sequence is higher (average 2.6-fold) than that observed at other loci. The
position of the human Xp/Yp telomere is unique, as additional sequences are
present at this location in the other three species. These included an
array of subterminal satellite in the chimpanzee and, in the gorilla a
small interstitial array of telomere-like repeats followed by sequences
with strong homology to the human 18p subterminal region. In the
orang-utan, two alleles with different structures were identified. These
differ by the presence or absence of a short interspersed nuclear element
(SINE) sequence just proximal to long arrays of telomere-like repeat
sequences that probably represent the proximal end of the orang-utan Xp/Yp
telomere. In addition, a high level of sequence divergence between the two
orang-utan structures was identified. This divergence is similar to that
observed between the human Xp/Yp telomere-adjacent haplotypes. The high
sequence divergence and evidence of gross rearrangements indicate that the
Xp/Yp telomeric region has evolved faster than the rest of the genome.
相似文献
127.
High throughput parallel analysis of hundreds of patient samples for more than 100 mutations in multiple disease genes 总被引:5,自引:0,他引:5
Shuber AP; Michalowsky LA; Nass GS; Skoletsky J; Hire LM; Kotsopoulos SK; Phipps MF; Barberio DM; Klinger KW 《Human molecular genetics》1997,6(3):337-347
As more mutations are identified in genes of known sequence, there is a
crucial need in the areas of medical genetics and genome analysis for
rapid, accurate and cost-effective methods of mutation detection. We have
developed a multiplex allele-specific diagnostic assay (MASDA) for analysis
of large numbers of samples (> 500) simultaneously for a large number of
known mutations (> 100) in a single assay. MASDA utilizes
oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA
samples are immobilized on a solid support and a single hybridization is
performed with a pool of allele-specific oligonucleotide (ASO) probes. Any
probes complementary to specific mutations present in a given sample are in
effect affinity purified from the pool by the target DNA. Sequence-specific
band patterns (fingerprints), generated by chemical or enzymatic sequencing
of the bound ASO(s), easily identify the specific mutation(s). Using this
design, in a single diagnostic assay, we tested samples for 66 cystic
fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell
anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations,
four mutations in Canavan disease, four mutations in Fanconi anemia, and
five mutations in BRCA1. Each mutation was correctly identified. Finally,
in a blinded study of 106 of these mutations in > 500 patients, all
mutations were properly identified. There were no false positives or false
negatives. The MASDA assay is capable of detecting point mutations as well
as small insertion or deletion mutations. This technology is amenable to
automation and is suitable for immediate utilization for high-throughput
genetic diagnostics in clinical and research laboratories.
相似文献
128.
Oocyte morphology predicts outcome of intracytoplasmic sperm injection 总被引:10,自引:14,他引:10
Serhal PF; Ranieri DM; Kinis A; Marchant S; Davies M; Khadum IM 《Human reproduction (Oxford, England)》1997,12(6):1267-1270
To examine the influence of cytoplasmic morphology on the success rate of
intracytoplasmic sperm injection (ICSI), the morphology of 837 metaphase II
oocytes was assessed after cumulus stripping. The main abnormalities
detected were excessive granularity, cytoplasmic inclusions such as
vacuoles, smooth endoplasmic reticulum clustering and refractile bodies.
Microinjection was performed in 538 oocytes with normal cytoplasm, 142 out
of 161 with excessive granularity and 112 out of 138 with cytoplasmic
inclusions. Very poor oocytes were not injected. No difference was found in
fertilization rate. The embryos achieved cleaved normally and a similar
number of good quality embryos among the three groups was noted. The
outcome of transfer of embryos derived solely from normal oocytes (group A:
72 patients, 183 embryos) was compared with those from oocytes with
cytoplasmic abnormalities (group B: 34 patients, 85 embryos). In group A,
17 clinical pregnancies (24% per patient, implantation rate 10%) were
established. In group B, only one clinical pregnancy (3% per patient,
implantation rate 1%) was established, from the transfer of embryos derived
from oocytes with homogeneous granularity of the cytoplasm. No pregnancy
resulted following the transfer of embryos from eggs with cytoplasmic
inclusions. The difference was statistically significant. The outcome of
ICSI is dependent on the quality of the oocytes retrieved. Normal
fertilization and early embryo development were achieved in oocytes with
abnormal cytoplasm morphology, but the resulting embryos failed to
demonstrate the same implantation potential as those derived from oocytes
with normal cytoplasm.
相似文献
129.
Kim YH; de Kretser DM; Temple-Smith PD; Hearn MT; McFarlane JR 《Molecular human reproduction》1997,3(4):307-313
Using mechanical and chemical dissection methods, fibrous sheath was
isolated both from normal ejaculated human spermatozoa and from rabbit
cauda epididymal spermatozoa. The same techniques did not produce a pure
preparation of fibrous sheath from ejaculated rabbit spermatozoa,
suggesting that further cross-linking and stabilization of sperm structures
occurs in response to components of the seminal plasma. The isolation
procedures were monitored by phase contrast microscopy and the purity of
the fibrous sheath was verified by electron microscopy. Sodium dodecyl
sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of isolated human
fibrous sheath revealed at least 14 protein bands of which the most
intensely stained were of molecular weight 84, 72, 66.2, 57, 32 and 28.5
kDa. The rabbit fibrous sheath revealed at least 10 protein bands, of which
the most intensely stained were 35.2, 32.7 and 28.5 kDa. The amino acid
composition of the purified fibrous sheath from human and rabbit
spermatozoa was similar, being high in aspartic acid and/or asparagine and
glutamic acid and/or glutamine, serine, alanine, leucine, lysine and
glycine, but low in histidine, tyrosine and isoleucine. This composition is
similar to that reported for the rat and suggests that mammalian sperm tail
fibrous sheaths are composed of similar types of proteins, although there
are apparent differences in protein components between species.
相似文献
130.
Serological responses to human papillomavirus type 6 and 16 virus-like particles in patients with cervical neoplastic lesions. 总被引:2,自引:0,他引:2 下载免费PDF全文
T Sasagawa M Inoue M Lehtinen W Zhang S E Gschmeissner M A Hajibagheri J Finch L Crawford 《Clinical and Vaccine Immunology : CVI》1996,3(4):403-410
Serum samples from 36 cervical carcinoma patients, 33 patients with high-grade squamous intraepithelial lesions, and 31 cytologically normal women were tested by enzyme-linked immunosorbent assay (ELISA) using human papilloma virus type 6 (HPV 6) and HPV 16 virus-like particles as antigens. Forty serum specimens from 1-year-old children were used to assign cutoff points. When serum samples from the subjects infected with HPV 16 were tested in an HPV 16 ELISA detecting immunoglobulin A (IgA), IgG, and IgM binding, 61% showed IgA, 44% showed IgG, and 39% showed IgM reactivity. Of HPV 6- or 11- or HPV 18-infected subjects. fewer than 17% showed IgA or IgG responses and 33% showed IgM reactivity. In contrast, 13% showed IgA, 10% showed IgG, and 16% showed IgM reactivity in the HPV DNA-negative controls. The results suggest that the IgA and IgG responses are HPV 16 specific and the IgM response is cross-reactive to different HPV types. On the other hand, the serological responses to HPV 6 did not differ in the patient and control groups. The percentages of patients positive for both IgA and IgG antibodies were significantly higher in the groups with high-grade squamous intraepithelial lesions (12% [4 of 33]; P = 0.04) and cancer (17% [6 of 36]; P = 0.02) than in the healty women (0% [0 of 31]), and the percentages for either IgA or IgG were higher for the cancer group (47% [17 of 36]; P = 0.01) than in the normal group (19% [6 of 31]). Most sera positive for IgA and IgG in the patient groups showed higher titers than those in the normal group. All these results suggest that high IgA and IgG responses are good indicators for estimating HPV 16 infection. 相似文献